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This  book  is  furnished  for  editorial 
purposes  by  the  New  York  publishers, 
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ON  INFANTILISM  FROM  CHRONIC 
INTESTINAL  INFECTION 


THE  MACMILLAN  COMPANY 

NEW  YORK   •    BOSTON   •    CHICAGO 
ATLANTA   •    SAN   FRANCISCO 

MACMILLAN  &  CO.,  Limited 

LONDON   •    BOMBAY   •    CALCUTTA 
MELBOURNE 

THE  MACMILLAN  CO.  OF  CANADA,  Ltd. 

TORONTO 


On  Infantilism  from 

Chronic  Intestinal 

Infection 


CHARACTERIZED  BY  THE  OVER- 
GROWTH AND  PERSISTENCE  OF 
FLORA  OF  THE  NURSLING  PERIOD 


A  Study  of  the  Clinical  Course,  Bacteriology,  Chemistry  and 
Therapeutics  of  Arrested  Development  in  Infancy 

BY 
C.  A.  HERTER,  M.D. 

Professor  of  Pharmacology  and  Therapeutics 
Columbia  University 


THE  MACMILLAN  COMPANY 

1908 

All  rights  reserved 


Copyright,  1908 
By  THE  MACMILLAN  COMPANY 


Set  up  and  electrotyped.    Published  November,  1908 


<PHE  MASON-HENRY  PRSSS 
8YRACUSK,  N.  Y. 


CONTENTS 

INFANTILISM    1 

The  Symptoms  and  Signs  of  Intestinal  Infantilism..  7 

(1)  Arrest  in  Development  of  the  Body 8 

(2)  Mental  Powers  and  Development  of   the  Brain 10 

(3)  Abdominal   Distension    11 

(4)  Anaemia    12 

(5)  Fatigue    13 

(6)  Disturbances  of   Intestinal  Function 14 

The  Bacterial  Flora  of  the  Intestinal  Tract 18 

(1)  Organisms  of  the  Bacillus  Bifidus  Type 23 

(2)  Organisms  of  the  Bacillus  Infantilis  Type 26 

(3)  Coccal    Forms    29 

The  Urinary  Expressions  of  Infection  Underlying  In- 
fantilism      33 

Features  Eelating  to  the  Intestinal  Contents 39 

The  Calcium  and  Magnesium  Balances 45 

The  Fat  Loss  by  the  Feces 48 

Pathology    , 53 

Eetardation    in    Development 54 

The  Acute  and  Subacute  Infections  Leading  to  Infan- 
tilism    75 

Mild  Types  of  Intestinal  Infantilism 77 

The  Sequelae  and  Prognosis  of  Intestinal  Infantilism  78 

The  Therapeutic  Modification  of  Bacterial  Conditions  81 

General  Hygienic  Measures 83 

Dietetic  Measures   86 

The   Carbohydrates    87 

The  Fats   91 

The   Proteins    94 

The  Use  of  Gelatin 96 

Pharmacological  Measures  106 

conclubions    112 

V 


430565 


V. 


INFANTILISM 

I  PKOPOSE  in  this  publication  to  describe  some 
of  the  leading  features  of  an  obscure  affection  of 
childhood  with  the  study  of  which  I  have  been  for 
several  years  engaged  but  of  whose  nature  I  have 
only  recently  been  able  to  form  a  reasonably  satis- 
factory conception.  This  pathological  state  is 
marked  by  a  striking  general  retardation  in  the 
growth  of  the  body  implicating  the  skeleton,  the 
muscles  and.  the  organs,  while  permitting  a  rela- 
tively fair  development  of  the  brain.  The  mate- 
rial on  which  the  present  description  is  based 
consists  of  five  cases  of  intestinal  infantilism 
which  I  regard  as  typical  and  fully  developed 
examples  of  this  distinctive  state.  And  in  addi- 
tion to  these  cases  I  have  studied  ^ve  others  of 
shorter  duration  and  subacute  course,  which  I  am 
disposed  to  consider  as  instances  of  intestinal 
infection  capable  of  giving  rise  to  pronounced 
infantilism  when  the  former  condition  has  per- 
sisted through  many  months.  With  the  exception 
of  two  of  the  cases  comprising  these  two  groups, 
I  owe  to  Dr.  L.  E.  Holt  the  opportunity  to  study 
these  patients.  He  has  helped  me  by  freely  plac- 
ing at  my  disposal  his  full  clinical  notes  and  by 

1  1 


2  INFANTILISM 

giving  me  access  to  his  patients.  In  several 
instances  the  patients  have  been  observed  by  Dr. 
Holt  and  myself  conjointly  during  a  period  of 
years  under  varying  dietetic  conditions.  The 
definite  character  of  the  symptom-complex  about 
to  be  described  has  long  been  recognized  by 
Dr.  Holt,  who  has  interested  me  in  the  present 
investigation. 

I  am  also  under  obligations  to  the  Eockefeller 
Institute  for  Medical  Eesearch,  especially  during 
the  past  year,  for  aiding  me  with  facilities  for 
engaging  in  the  extremely  complex  bacteriologi- 
cal problems  with  which  this  study  was  beset. 
I  am  especially  indebted  to  Mr.  A.  I.  Kendall, 
Fellow  of  the  Eockefeller  Institute,  for  technical 
help. 

It  has  not  been  possible  to  investigate  with 
equal  thoroughness  all  the  cases  of  intestinal  in- 
fantilism that  constitute  the  basis  of  this  publica- 
tion. In  some  instances  attention  has  been  given 
especially  to  certain  limited  aspects  of  the  patho- 
logical i)roblem,  while  in  other  cases  study  has 
been  especially  focused  on  other  features;  but  in 
three  instances  the  investigations  have  had  a  wider 
and  more  representative  aim.  In  two  of  these  three 
instances  the  patients  have  been  under  my  per- 
sonal observation  during  periods  of  many  months, 
and  through  close  attention  it  has  been  possible 
to  detect  and  to  follow  with  unusual  detail  numer- 
ous manifestations  of  the  morbid  process.    I  shall 


INFANTILISM  3 

not  undertake  in  the  present  publication  to  give 
full  individual  histories  of  the  cases  observed,  but 
shall  merely  give  very  brief  outlines  embodying 
the  chief  clinical  data,  and  to  these  outlines  such 
references  will  be  made  from  time  to  time  as  may 
serve  to  illustrate  the  various  points  under  dis- 
cussion. 

Case  I.    Male,  aet.  8  years.    Older  sister  in  good  health.    ISTor- 
mal   infancy  with   average    growth.     During    third   year   reached 
weight  of  31  lbs.     At  this  time  irregularities  of  digestion,  especi- 
ally periods  of  diarrhoea  with  mucus.     Gradual  loss  of  weight, 
increasing    abdominal    distension,    carbohydrate    intolerance    and 
fat  diarrhoea.     Between  third  and  seventh  years  weight  did  not 
exceed  31  lbs.     Usually  losses  in  summer,  gains  in  winter,  weight 
usually  between   25   and  28  lbs.     Moderate  anaemia.     Increasing 
lassitude.      Drowsiness    during    day.      Walking    dif&cult.      Eapid 
onset  of  fatigue.     Peevishness,  emotional  instability,  slight  signs 
of  rickets.     Appetite  nearly  always  keen.     Many  dietetic  experi- 
ments tried  between  third  and  seventh  years  with  little  success. 
Movements  several  daily,  soft,  voluminous,  gray,  fatty,  gaseous, 
odor    indolic,   reaction   usually   slightly   acid    or   neutral.      Mucus 
variable,  at  times  very  abundant,  in  masses  on  surface  or  mixed 
with  feces.    Urine  rich  in  indican  and  phenol.     Aromatic  oxyacids 
not  markedly   excessive.     During   last  year   gradual    decrease   in 
indican.     Eeactions  for  indolacetic  acid  very  marked.     November, 
1907,  weight,  25  lbs. ;  height,  36  ins.    Careful  dietetic  and  hygienic 
measures  instituted.     Next  four  months  slight  gains  and  losses  in 
weight  but  no   material   improvement   in   weight   though  decided 
improvement  in  character  and  frequency  of  stools  and  diminution 
in  signs  of  intoxication.     From  March,  1907,  to  July,  1908,  unin- 
terrupted somewhat  uneven  gain  in  weight  to  31  lbs.    Also  gain  in 
height  (about  li/g  inch).     Movements  became  entirely  normal  in 
color,  consistence  and  frequency.     Urine  shows  striking  reduction 
in  putrefactive  products.     Mental  and  emotional  condition  greatly 
improved.       Expression     animated.       Physical     activity     greatly 
increased,   walking   fair    for    considerable    distances.     Abdominal 
distension  much   diminished.     During  past   six  months  there  has 
been  a  radical  alteration  in  the  bacterial  flora  of  the  large  intes- 


4  INFANTILISM 

tine,  marked  by  the  establishment  of  B.  lactis  aerogenes  and  B. 
coll.  Still  remains  very  sensitive  to  carbohydrates,  even  a  slight 
increase  being  quickly  followed  by  large  fermentative  movements. 
Under  such  conditions  the  child  ceases  to  gain  weight  and  there 
is  a  return  of  coccal  forms  in  the  feces,  but  B.  Mfidus  cannot  be 
detected.  Such  a  temporary  interruption  in  growth  occurred  dur- 
ing August,  1908. 

Case  II.  Female,  aet.  9  years.  Two  older  children,  always 
well.  Normal  infancy,  nursed  during  early  months.  At  end  of 
second  year  irritant  medication  followed  by  gastritis  lasting 
several  days  and  only  slowly  subsiding.  Present  illness  dates 
from  this.  Slight  signs  of  rickets  somewhat  antecedent  to  the 
gastritis.  By  third  year  nutrition  was  impaired  and  development 
became  much  retarded.  Child  markedly  undersized,  head  slightly 
rachitic,  digestive  tract  irritable,  carbohydrates  very  badly 
tolerated,  fat  absorption  much  impaired,  abdomen  much  distended. 
By  fourth  year  walking  still  very  imperfect  and  child  much 
undersized.  Weight  at  this  time  not  recorded,  but  nutrition 
much  impaired  and  remained  so  during  fourth,  fifth,  and  sixth 
years.  Throughout  this  time  there  were  moderate  anaemia,  fat 
diarrhoea,  grayish,  voluminous,  gas-holding,  indolic  stools.  Urine 
regularly  gave  intense  indican  reactions.  Ethereal  sulphates, 
phenols  and  aromatic  oxyacids  regularly  much  increased,  micturi- 
tion often  extremely  frequent.  During  this  entire  period  emo- 
tional instability,  peevishness,  great  physical  langour,  walking 
quickly  followed  by  fatigue.  In  sixth  year,  after  more  than  a 
year  of  careful  regulation  of  diet,  gradual  improvement  in  nutri- 
tion, and  gain  in  physical  strength  with  slow  disappearance  of 
neuromuscular  disorders.  Simultaneously  gradual  diminution  of 
putrefactive  products  in  urine  and  pronounced  improvement  in 
feces,  which  became  formed,  colored,  of  normal  fat  content  and 
nearly  free  from  indol  and  phenol.  Gradual  appearance  of 
B.  lactis  aerogenes  and  B.  coli  in  large  numbers  in  the  feces. 
At  six  and  one-half  years  weight  rose  to  45  lbs.  During  next 
year  gained  2  lbs.  During  following  year  gained  10  lbs.,  to 
58  lbs.  During  last  six  months  gained  7  lbs.  with  rapid  gain  in 
stature.  Onset  of  epileptiform  seizures  during  this  period  with 
return  of  putrefactive  products  in  urine. 

Case  III.  Female,  aet.  about  7  years.  Under  observation 
together  with  Dr.  L.  E.  Holt  for  past  3  years.  When  first  seen, 
greatly  emaciated.  Abdomen  much  distended,  superficial  veins 
distended   markedly.     Skin   white   and   wrinkled.     Anaemia  mod- 


INFANTILISM  5 

erate.     Head   slightly   rachitic,   well    developed.     Extremely    emo- 
tional    and     peevish,     but     intelligent.     Movements     voluminous, 
acholic    in  appearance,   usually   two   or   three   daily;    odor   putre- 
factive   (indolic),   reaction   usually   neutral   or   acid.     Fatty   acid 
crystals  very   abundant,   mucus  variable,   indol  regularly  present, 
phenol  sometimes.     Diarrhoea  easily  provoked  by  use  of  carbohy- 
drates.    Urine   frequently  voided,   indican   abundant,   phenol   and 
aromatic   oxyacids   excessive.     Eecord   of    weight   lost,   but    child 
much  beneath  average  weight  for  about  one  year  before  observa- 
tion.    Loss   in  weight   dates   from   middle   of    third   year,   when 
irregular  diarrhoea  and  large  movements  became  chronic.     During 
first  two  years  under  observation  only  slight  gain  in  weight,  but 
some  improvement  in  movements,  which  became  seldom  diarrhoeal 
but  remained  voluminous.     During  past  year  more  rapid  gam  in 
weight,  but  still  markedly  under  weight.     Case  closely  resembles 
Case  I,  but  infantilism  is  somewhat  less   pronounced  in   degree. 
Conditions    for    dietetic    treatment   much   less    favorable   than   in 
Case  I.     Outlook  is   now   for   decided  permanent   retardation  m 
growth.     Child  was  normal  at  birth  and  for  first  two  years. 

Case  IV.     Male,  aet.  3  years.     Normal  weight  at  birth,  nursed 
6    weeks.     Modified    milk.     Did   well  first   year.     Then   irregular 
intestinal    troubles,     diarrhoea    with    mucus.     Marked     anaemia 
gradually  developed   (Hb  35%)   vnth  great  abdominal  distension. 
Appetite    poor.     Peevishness.     Slow    loss    in    weight    from    16th 
month.     Movements  gray,  voluminous,  pasty.     Fatty  acid  crystals 
extremely  abundant,  indol,  but  no  skatol;  phenol  at  times.    Urme, 
much  indican  usually,  also  excess  phenols  and  aromatic  oxyacids. 
Many  experiments  with  diet;  peptonized  milk;  kumyss,  egg  white, 
rare    scraped    meat.    Nestle 's    Food,    etc.     Appetite    capricious. 
Weight  at  20  mos.,  16  lbs.;  height,  3034  inches;  at  27  mos.,  lo  lbs. 
Gradually  gained  to  17  lbs.  then  acute  slight  enterocolitis  for  4  or 
5  days.     Gradually  lost  weight  to  less  than  15  lbs.     At  33  mos., 
weight,    16%    lbs.;    height,    31    inches.     Hb.    34%.     Very    slow 
improvement  in  weight  and  movements.     Now    (3  years)    18  lbs. 
and  Hb.   61%.     Appetite  never   satisfied,   tongue   clean   and  red. 
Abdominal    distension    persists.     Spirits    improved.     Tendency    to 
diarrhoea  from  carbohydrates  continues.     Milk  remains  basis  of 
diet.     Improvement  probably  delayed  by  impracticability  of  fol- 
lowing patient  closely.  x^    tt  u 
Case  V.    Female,  aet.  9i/o  years.     Patient  of  Dr.  L.  E.  Holt. 
Third  of  four  children;    others  healthy.     Partly  nursed   3  mos., 
did   poorly,   was    weaned.     Fed    on    sterilized   milk,    cream,    lime- 


6  INFANTILISM 

water  rest  of  first  year.  Did  only  fairly  well;  fat  but  pale. 
Measles  at  18  mos.;  mild.  Vaccinated  at  2  years;  sore  healed 
normally.  With  vaccination,  vomiting  and  fever.  Troubles  of 
digestion  rather  marked  ever  since.  Vomiting  and  fever  rarely, 
but  tendency  to  soft  movements  and  diarrhoea  with  occasional 
constipation.  During  fifth  and  sixth  years  marked  irregularities 
of  bowels  associated  with  efforts  to  increase  diet.  Seizures  of 
loss  of  appetite,  headache  and  loss  in  weight,  light-colored  stools, 
lasting  several  weeks.  Marked  abdominal  distension,  tongue 
coated,  breath  not  good.  Food,  milk,  a  little  bread,  beef  juice. 
With  every  effort  to  give  carbohydrates  child  shows  digestive 
derangements  after  a  few  days.  At  51/2  years,  weight,  21%  lbs.; 
height,  35  inches.  Very  pale,  spleen,  liver,  glands  palpate  normal, 
tongue  slightly  coated,  abdomen  smaller  than  formerly;  a  small, 
pathetic,  delicate  little  child  with  no  animation.  Sometimes  does 
not  walk  for  2  or  3  months.  Eemained  very  much  under  weight 
until  nearly  9  years  old,  with  periods  of  great  abdominal  dis- 
tension and  continued  intolerance  for  carbohydrates  and  fats. 
Constipation  at  times,  owing  probably  to  milk  diet.  Facial 
neuralgia  frequent,  anaemia  marked.  Great  listlessness.  Walks 
only  a  few  steps  about  the  house.  Appetite  always  excellent  now, 
could  take  much  more  but  cannot  tolerate  increased  food.  Milk 
agrees  best.  Diet  somewhat  enlarged  with  barley  broth,  baked  potato, 
butter,  tapioca  pudding.  On  this  diet  good  gain  in  weight  lately. 
Gain  to  33  lbs.  at  914  years  and  rather  rapid  gain  in  height  to 
38iy4  inches.  Head  20  inches,  somewhat  rachitic,  flat  type  and 
large  parietal  bones.  Morbid  appetite  for  chalk,  dirt,  cigar 
ashes,  pencils,  etc.  Urinary  indications  of  intestinal  putrefaction 
but  slight.  Anaemia  still  marked.  This  case  of  intestinal  infan- 
tilism is  of  somewhat  different  type  from  the  others  in  this  group. 
Less  indication  of  ordinary  indolic  putrefaction,  more  tendency 
to  anaemia.  Uncertainty  as  to  pathology  from  standpoint  of 
bacterial  flora. 

The  symptom-complex  which  I  wish  to  de- 
scribe is  so  clearly  definable  that  few  physicians 
with  a  practice  among  children  will  fail  to 
recognize  a  few  instances  of  this  unmistakable 
and  extreme  manifestation  of  a  morbid  nutri- 
tional process.     I  shall  group  under  the  follow- 


INFANTILISM  7 

ing  heads   the  facts  and  views   which  I   desire 
to   present. 

1.  The    Symptoms    and    Signs    of    Intestinal 

Infantilism. 

2.  The    Bacterial    Flora    of    the    Intestinal 

Tract  in  Cases   of  Infantilism. 

3.  The  Urinary  Expressions  of  the  Infection 

underlying  Infantilism. 

4.  The   Pathology  of   Intestinal   Infantilism. 

5.  The  Acute  and   Subacute  Infections  lead- 

ing  to   the   Establishment   of   Intestinal 
Infantilism. 

6.  Mild  Types  of  Intestinal  Infantilism. 

7.  The  Sequelae  and  Prognosis  of  Intestinal 

Infantilism. 

8.  The  Therapeutic  Modification  of  the  Bac- 

terial Conditions  in  Intestinal  Infantilism. 

The   Symptoms   and   Signs  of   Intestinal 
Infantilism 

The  patients  comprising  the  group  of  the 
type  of  fully  developed  infantilism  which  I 
desire  to  describe  varied  from  four  to  six  years 
of  age  at  the  time  when  they  first  came  under 
observation.  In  each  case  the  child  had  been 
ill  for  one  year  or  longer  at  the  time  of  its 
first  observation  by  Dr.  Holt  or  by  myself,  and 
had  suffered  from  pronounced  irregularities 
referable  to  the  digestive  tract.  In  each  case 
there    was    a  history    of   periods    of    disturbed 


8  INFANTILISM 

nutrition  with  loss  of  weight  alternating  with 
periods  of  improvement  in  nutrition  and  gain 
in  weight.  But  these  variations  ultimately  cul- 
minated in  each  case  in  a  state  in  which  there 
was  apparently  a  complete  arrest  of  develop- 
ment, and  although  obvious  symptoms  of  di- 
gestive disturbance,  such  as  diarrhoea,  were 
checked  by  suitable  treatment,  there  remained 
an  arrest  in  growth  and  the  utmost  difficulty 
was  experienced  in  securing  any  noteworthy 
increase  in  weight. 

The  clinical  features  characteristic  of  pro- 
nounced infantilism  may  be  divided  into  two 
groups,  the  chief  or  essential  clinical  features 
and  the  minor  or  accessory  features. 

The  chief  or  essential  clinical  features  are 
the  following:  (1)  an  arrest  in  the  development 
of  the  body;  (2)  the  maintenance  of  mental 
powers  and  fair  development  of  the  brain; 
(3)  marked  abdominal  distension;  (4)  moderate 
grade  of  anaemia;  (5)  rapid  onset  of  physical 
and  mental  fatigue;  (6)  various  obtrusive  irregu- 
larities referable  to  the  intestinal  tract.  These 
features   may  be   considered  in  turn. 

(1)  Arrest  in  Development  of  the  Body.  The 
arrest  in  development  is  the  most  striking 
feature  of  these  cases.  In  Case  I  the  patient 
at  the  age  of  seven  years  weighed  only  25  pounds^ 

^  Holt  gives  the  weight  for  a  boy  of  two  years  as  26.5  pounds. 
The  weight  at  seven  years  should  not  be  far  from  50  pounds, 


INFANTILISM  9 

and  had  a  height  of  only  36  inches.^  In 
Case  V  the  patient  at  the  age  of  nine  years 
weighed  only  29  pounds.  In  this  case  the  child 
was  first  observed  at  a  time  when  some  im- 
provement had  set  in,  a  gain  of  two  pounds 
having  been  made  in  the  course  of  the  past 
year,  but  previous  to  this  time  the  patient  had 
for  some  time  remained  in  a  stationary  con- 
dition as  regards  weight  and  development.  In 
Case  II  there  was  a  period  of  about  two  years 
(from  the  third  to  the  fifth  year)  in  which 
there  was  a  striking  arrest  of  development, 
and  the  maintenance  of  a  nearly  stationary 
weight  despite  the  fact  that  the  utmost  care 
was  taken  to  insure  dietetic  conditions  favor- 
able to  an  improvement  in  growth.  In  the  two 
remaining  cases  exact  data  are  lacking,  but  in 
both  instances  retardation  of  growth  was  a 
striking  feature  during  a  long  period  of  time. 
In  several  instances  it  was  noticed  that  there 
was  a  slight  tendency  to  improvement  in  weight 
during  the  winter  months,  this  tendency  to 
improve  being  more  than  overbalanced  by  losses 
made  during  the  summer.  These  losses  in 
weight  were  always  attributable  to  an  increase 
in  disturbances  referable  to  the  intestinal  func- 
tions and  were  commonly  associated  with 
diarrhoea.  This  diarrhoea  was,  however,  not 
necessarily  very   pronounced   or   of  long   dura- 

*  Thirty-five  inches  is  the  height  given  for  three  years. 


10  INFANTILISM 

tion,  and  often  consisted  rather  in  an  excessive 
softening  of  the  intestinal  contents  and  increase 
in  mncns  than  in  an  acnte  watery  diarrhoeal 
condition 

(2)  The  Maintenance  of  Mental  Potvers  and 
Fair  Development  of  the  Brain.  It  is  note- 
worthy that  despite  the  retardation  in  the 
general  development  of  the  organism,  the  brain 
is  fairly  well  developed  in  all  of  the  cases  of 
infantilism  nnder  observation.  Thns  in  Case  I, 
although  the  height  was  only  36  inches  and 
the  weight  25  ponnds,  the  circumference  of  the 
head  was  20  inches.^  Entirely  comparable  con- 
ditions were  noted  in  the  other  cases.  The 
intelligence  of  these  patients  was  in  every 
instance  good,  and  contrasts  very  strikingly 
with  the  bad  physical  development.  Of  course 
these  children  are  all  defectively  educated  owing 
in  part,  at  least,  to  the  physical  retardation 
which  makes  it  inadvisable  or  impossible  to 
secure  even  the  ordinary  educational  oppor- 
tunities. It  is  noteworthy  that  in  all  of  these 
children  there  was  a  certain  slowness  of  mental 
action  and  perhaps  a  somewhat  greater  thought- 
fulness  than  is  usual  in  children  of  their  age. 
In  replying  to  questions  these  children  have 
often  shown  some  irritability  and  peevishness, 
and   in   several   instances   I   think   there   is    no 

*Holt  gives  19.7  inches  for  the  circumference  of  the  male  head 
at  four  years;  20.5  inches  at  five  years. 


INFANTILISM  11 

doubt  that  the  mental  processes  subserving 
self-preservation  were  more  than  usually  acute 
for  children  of  their  ages.  It  is  possible  that 
this  was  the  result  of  the  isolation  to  which 
all  of  these  patients  had  been  subjected  and 
of  an  inability  to  enter  into  the  play  of  chil- 
dren of  the  same  age.  The  necessity  for  living 
very  carefully  and  obeying  the  directions  of 
the  physician  and  nurse  has  tended  to  make 
these  children  somewhat  introspective  as  regards 
their  own  ailments  and  to  form  the  basis  of 
what  might,  with  increasing  consciousness, 
develop  in  after  life  into  a  hypochrondriacal 
condition.  In  all  of  the  patients  periods  of 
langour  have  been  very  noteworthy  during  the 
time  of  arrested  physical  development.  Fre- 
quently for  hours  at  a  time  they  show  little 
or  no  desire  to  play  or  to  speak  and  their 
faces  at  these  times  look  pinched  and  distressed. 
There  has  been  no  difficulty  in  any  of  these 
cases  in  teaching  the  children  to  be  cleanly, 
and  there  is  no  doubt  that  what  they  have 
lost  in  the  direction  of  spontaneity  and  play- 
fulness, as  the  result  of  disease,  has  been  in 
a  measure  compensated  by  an  improved  self- 
control,  which,  in  the  case  of  diet,  has  come  to 
amount  almost  to  automatism. 

(3)  Marked  Abdominal  Distension,  Marked 
abdominal  distension,  due  in  part  to  a  dis- 
tension   of    the    colon   with    gas    and    probably 


12  INFANTILISM 

also  to  distension  of  the  small  intestine,  has 
been  a  feature  of  these  cases.  The  distension 
has  varied  somewhat  from  time  to  time,  but 
there  have  been  long  periods  in  each  case  in 
which  the  distension  showed  little  variation  and 
a  return  to  normal  abdominal  conditions  was 
never  witnessed.  As  these  patients  gradually 
improved  in  physical  condition  under  suitable 
dietetic  treatment,  the  distension  gradually 
became  less.  This  condition  of  distension,  when 
once  established,  is  not  necessarily  accompanied 
by  any  intestinal  or  gastric  flatulence  in  the 
sense  of  actual  passing  of  considerable  quanti- 
ties of  gas.  It  appears  that  the  abdominal 
distension  was  preceded  in  each  case  by  a  period 
in  which  gas  formation  had  been  active  and 
flatulence  pronounced,  but  that  after  a  time 
partial  paralysis  of  the  gut  sets  in,  which  per- 
mits the  accumulation  of  gas  even  though  the 
latter  be  not  necessarily  formed  in  great  excess. 
The  abdominal  veins  are  frequently  markedly 
dilated,  especially  over  the  upper  part  of  the 
abdomen. 

(4)  Moderate  Anaemia.  In  all  of  the  ^yq 
cases  of  infantilism  which  were  studied,  mod- 
erate anaemia  was  a  feature.  The  haemoglobin 
was  diminished  to  75-60  per  cent,  in  Cases  I, 
II  and  III  without  a  corresponding  diminution 
in  the  number  of  red  blood  cells.  In  two 
instances,    however     (Cases    IV    and    V),    the 


INFANTILISM  13 

anaemia  was  considerably  more  pronounced,  and 
in  Case  V  was  a  long  persistent  feature  of  the 
disease.  In  the  latter  instance  the  haemoglobin 
was  at  one  time  only  22  per  cent.,  and  there 
was  a  moderate  diminution  in  the  number  of 
red  blood  cells.  In  all  of  these  cases  there  is 
reason  to  think  that  the  volume  of  blood  is  at 
least  moderately  below  what  it  should  be  for 
a  child  of  the  same  weight.  This  suspicion  is 
based  on  the  pallor  of  the  body  and  the 
extremities,  which  may  be  much  out  of  propor- 
tion to  the  fall  in  haemoglobin.  The  white 
blood  cells  were  examined  in  Case  I.  No  note- 
worthy departures  from  the  normal  were  noted.^ 

Leucocytes  5000 

Small  mononuclears   33% 

Large  mononuclears 1% 

Eosinophiles     1% 

Polymorphonuclears    62% 

Transitionals    3% 

An  examination  made  on  April  22,  1908,  gave  the  foUowirig: 
Leucocytes  6000 

Small  mononuclears   35%      Polymorphonuclears    51% 

Large  mononuclears 2%      Myelocytes    6% 

Eosinophiles     3%      Transitionals    3% 

(5)  Rapid  Onset  of  Fatigue.  A  character- 
istic feature  of  these  cases  of  infantilism  is 
the  rapid  onset  of  muscular  fatigue.  Indeed, 
it  would  probably  be  more  accurate  to  say 
that   the   muscles   are   never  thoroughly   rested 

*  An  examination   made   Dec.   30,   1907,  by  Dr.  Baldwin  gave 
the  following  results: 


14  INFANTILISM 

and  that  a  state  of  fatigue  is  cliroiiic.  The 
older  children,  at  the  height  of  the  develop- 
mental arrest,  are  unable  to  walk  more  than  a 
few  blocks  without  being  thoroughly  tired. 
They  are  also  unable  to  walk  up  and  down 
stairs.  Learning  to  walk  is  a  slow  and  dis- 
couraging process.  In  Case  II  the  child  did 
not  learn  to  stand  until  it  was  more  than  four 
years  old,  up  to  which  time  it  crept  languidly 
on  the  floor.  During  the  fifth  year  it  learned 
to  walk  with  great  difficulty.  Essentially  the 
same  condition  existed  in  Cases  III,  IV  and 
V.  It  is  to  be  noted  that  the  muscles  are  soft 
and  flabby  in  these  cases  of  infantilism.  The 
readiness  with  which  mental  fatigue  comes  on 
has  already  been  commented  upon.  As  will  be 
seen  later  in  a  discussion  of  the  pathology  of 
this  condition,  there  is  good  evidence  for  believ- 
ing that  both  the  muscular  and  mental  fatigue 
are  the  result  of  a  chronic  intoxication. 

(6)  Disturbances  of  Intestinal  Function.  One 
of  the  most  striking  and  characteristic  features 
of  infantilism  has  to  do  with  the  disturbance 
incidental  to  intestinal  function.  Although  such 
disturbances  may  be  reduced  to  a  minimum 
through  very  careful  feeding,  the  dietaries  of 
these  children  are  usually  such  when  they  come 
under  the  observation  of  physicians  that  they 
show  very  obvious  disorders  of  function.  Diar- 
rhoea was  a  feature   of  all  of  the  cases  with 


INFANTILISM  15 

whicli  this  report  deals.  Pronounced  watery 
diarrhoeal  attacks  are,  however,  comparatively 
rare.  Much  more  frequent  are  the  disturbances 
manifesting  themselves  by  the  appearance  of 
soft  stools  containing  an  abundance  of  neutral 
fat,  soap  and  fatty  acid  crystals.  The  excess 
of  fat  is  often  sufficiently  great  to  constitute 
a  condition  of  true  steatorrhoea,  if  thereby  we 
imply  a  loss  of  fat  serious  to  nutrition.  Dur- 
ing a  part  of  the  time  the  stools  are  not  of 
abnormal  frequency.  Nevertheless  they  contain 
an  excess  of  fat  unless  the  diet  is  especially 
regulated  with  a  view  to  reducing  its  fat  con- 
tent. During  exacerbations  of  the  diarrhoeal 
disturbance  the  patients  are  in  especially  poor 
condition,  losing  weight  and  suffering  from 
cold  hands  and  feet  and  showing  a  pinched 
appearance.  These  diarrhoeal  disorders,  though 
often  of  short  duration,  may  also  cause  marked 
prostration,  and  on  many  days  patients  are  so 
much  enfeebled  as  to  get  about  with  greatly  in- 
creased difficulty.  With  the  cessation  of  the 
diarrhoea  there  is  a  tendency  to  rapid  recovery, 
although  a  loss  in  weight  of  half  a  pound  or 
a  pound  may  not  be  regained  for  several  weeks. 
The  details  relating  to  the  morphological  and 
chemical  characters  of  the  intestinal  contents 
will  be  discussed  in  another  section  of  this 
paper. 


16  INFANTILISM 

Among  the  minor  or  accessory  clinical  fea- 
tures observed  in  our  cases  of  infantilism  are 
to  be  included  sweating  about  the  head  during 
sleep,  excessive  appetite,  somewhat  excessive 
thirst  and  consequent  increase  in  the  urine, 
various  indications  of  nervous  instability  and 
an  habitually  subnormal  temperature  with  cold 
and  pale  hands  and  feet.  In  three  of  the  cases 
(Cases  I,  II  and  V)  the  sweating,  especially 
of  the  skin  of  the  head,  was  for  a  time  well 
marked,  but  this  symptom  very  soon  disappeared 
with  return  of  strength.  An  excessive  appe- 
tite, at  least  at  certain  times,  was  a  feature 
in  all  the  cases.  Occasionally,  especially  dur- 
ing the  diarrhoeal  periods,  there  is  loss  of 
appetite.  But  the  maintenance  of  a  large  appe- 
tite is  a  feature  in  these  cases.  A  similar 
readiness  to  take  food  has  been  noticed  in  the 
subacute  affections  which,  beginning  in  early 
infancy,  lead  to  the  state  of  infantilism.  The 
abnormal,  sometimes  even  voracious,  appetite 
is  probably  due  to  the  condition  of  chronic 
enteritis  which  exists  in  these  patients  and  is 
probably  similar  in  its  origin  to  an  increase 
in  appetite  observed  in  some  neurasthenic 
adults.  The  nervous  instability  is  shown  in 
some  of  these  patients  by  rapid  variations  in 
temper  from  insignificant  causes.  In  one  in- 
stance (Case  I)  there  was  also  a  tendency  to 
urticarial  outbreaks,  which  occurred  from  time 


INFANTILISM  17 

to  time  without  definitely  assignable  cause. 
In  another  case  (Case  II)  there  developed 
attacks  of  petit  mat  which,  as  will  afterwards 
be  more  fully  stated,  gave  way  to  epileptiform 
seizures  of  grand  mal. 

In  four  of  the  ^yq  cases  of  infantilism  there 
were  very  slight  indications  of  rickets,  but  it 
may  be  said  in  general  that  the  signs  of 
rickets,  if  present  at  all,  do  not  form  part  of 
the  symptom-complex  at  present  under  discus- 
sion. Outside  the  present  group  I  have  seen 
well-marked  instances  which  showed  no  signs 
of  rickets.  There  are  no  striking  pulmonary 
or  circulatory  peculiarities  in  these  cases.  The 
pulse  is  usually  regular  when  the  patients  are 
quiet,  of  low  tension  and  small  in  volume. 
The  pulse  is  unduly  accelerated  by  slight  acti\dty 
or  slight  exterior  nervous  stimuli.  Abnormalities 
of  the  spleen,  liver  or  thyroid  have  not  been 
detected.  In  one  case  (Case  I)  there  was  slight 
enlargement  of  the  posterior  cervical  glands. 
A  status  of  blood  occurs  readily  in  artificially 
congested  areas  of  the  skin — an  effect  like  that 
of  the  so-called  meningeal  streak  being  readily 
produced.  The  tongue  is  apt  to  be  somewhat 
more  red  than  normal,  and  the  papillae  swollen, 
but  in  none  of  our  cases  was  there  any  denu- 
dation of  epithelium  or  any  indication  of  the 
occurrence  of  geographical  tongue.     The  tongue 

2 


18  INFANTILISM 

is    at   times   slightly   swollen   and   on  its   edges 
marked   by  impressions   of   the   teeth. 

The  Bacterial  Floea  of  the  Intestiitai.  Tract 
IN    Cases    op   Infantilism 

The  difficnlties  that  lie  in  the  way  of  the 
adequate  understanding  of  the  bacterial  con- 
ditions of  the  digestive  tract  have  been  in  gen- 
eral so  numerous  as  to  discourage  attempts  to 
investigate  the  nature  of  the  flora  in  chronic 
diseases  of  the  intestine.  Of  these  difficulties 
there  are  three  which  are  specially  obvious, — 
first  the  multiplicity  of  the  floral  types;  sec- 
ondly, the  imcertainty  of  cultivating  the  really 
dominant  organisms;  third,  the  difficulty  of 
obtaining  for  study  those  products  of  symbiotic 
bacterial  action  which  are  truly  representative 
of  the  decompositions  which  occur  in  the  intes- 
tine. Although  efforts  have  been  made  in  the 
present  study  to  overcome  these  obstacles,  these 
efforts  have  been  only  in  part  successful.  Still 
it  is  fair  to  say  that  the  methods  of  investi- 
gation employed  have  yielded  a  helpful  if  not 
satisfying  conception  of  the  processes  that  hold 
sway  in  the  digestive  tract  in  the  state  of 
infantilism.  It  is  not  intended  to  discuss  in 
detail  in  the  present  communication  the  methods 
of  investigation  employed,  nor  to  describe  fully 
the  characters  of  the  organisms  which  have 
been  found  to  dominate  the  intestinal  flora.   In 


INFANTILISM  19 

many  directions  the  details  concerning  the 
nature  of  the  organisms  which  have  been  found 
to  be  dominant  in  these  cases  have  not  been 
established  with  sufficient  precision.  Knowl- 
edge is  especially  scanty  at  the  present  time  in 
regard  to  the  biochemical  activities  of  certain 
of  the  organisms  that  have  been  found  to 
dominate  the  intestinal  tract  in  these  cases. 
Especially  is  knowledge  lacking  in  regard  to 
the  products  of  symbiotic  growth  of  the  chief 
organisms  observed.  For  the  present  purpose 
it  will  suffice  to  state  that  the  methods  of  bac- 
terial study  which  have  proved  most  service- 
able in  this  investigation  have  been  (a)  the 
study  of  the  Gram-stained  fecal  fields;  (h)  the 
study  of  the  sediments  of  the  sugar-bouillon 
and  plain  bouillon  tubes  after  inoculation  with 
the  mixed  fecal  flora;  (c)  a  variety  of  aerobic 
and  anaerobic  cultural  procedures  involving  the 
use  of  many  kinds  of  media  made  necessary 
by  the  difficulty  of  growing  certain  species  of 
bacteria  in  pure  culture.^  In  these  studies  bac- 
teria were  obtained  not  only  from  the  feces, 
but  from  material  derived  by  the  use  of  calomel 
catharsis  from  the  upper  levels  of  the  intes- 
tine. Such  catharsis  failed,  however,  in  general, 
to  show  radical  differences  between  the  bacterial 

*  In  the  case  of  one  of  the  microorganisms  to  be  described 
(B.  infantilis)  careful  studies  were  made  of  the  products  of 
growth.  The  results  will  be  separately  published  in  conjunction 
with  Mr.  Kendall. 


20  INFANTILISM 

types  so  obtained  and  those  obtained  from  the 
feces,  despite  the  fact  that  coccal  and  Gram- 
negative  forms  were  usually  obtained  in  greater 
abundance  from  these  upper  regions.  A  dis- 
tinction of  greater  significance  was  found  to 
relate  to  differences  noted  between  the  bacteria 
derived  from  the  fecal  masses  and  those  derived 
from  the  mucous  membrane  of  the  intestine. 
To  these  differences  further  reference  will  be 
made.  About  three  years  ago,  while  studying 
a  patient  with  intestinal  infantilism,  I  observed 
that  the  Gram-stained  fecal  fields  were  regu- 
larly made  up  of  almost  exclusively  Gram- 
positive  microorganisms.  These  positive  bac- 
teria were  almost  exclusively  slightly  curved 
rods  from  two  to  three  microns  in  length  and 
about  one-half  micron  in  diameter.  The  ends 
of  these  rods  were  sometimes  rounded  and 
sometimes  pointed.  Morphologically  similar 
fields  are  sometimes  observed  in  normal  breast- 
fed children  as  has  been  noted  by  Tissier, 
Moro  and  others.  But  while  it  may  be  re- 
garded as  entirely  normal  to  find  organisms 
of  this  character  in  a  certain  proportion  of 
healthy,  breast-fed  children,  it  was  surprising 
to  find  organisms  of  this  nature  as  the  domi- 
nant bacteria  in  children  five  or  six  or  even 
eight  years  of  age.  The  study  of  normal  chil- 
dren at  these  ages  has  failed  to  give  any  such 
pictures  as  those  which  I  have  noticed  in  the 


INFANTILISM  '  21 

group  of  cases  of  infantilism  now  under  con- 
sideration. Similar  organisms  have,  however, 
been  observed  in  the  Gram-stained  fields  in  a 
group  of  young  children  fed  on  cow's  milk 
and  suffering  from  pronounced  acute  or  sub- 
acute gastro-enteritis.  As  I  shall  point  out 
later,  it  appears  highly  probable  that  the  cases 
of  chronic  infantilism  have  their  origin  in 
intestinal  disorders  of  very  early  life  charac- 
terized by  the  presence  of  dominant  Gram- 
positive  flora  of  the  kinds  above  described. 

The  nature  of  these  Gram-positive  organisms, 
which  constitute  so  persistent  and  dominant  a 
feature  in  our  cases  of  infantilism  when  at  the 
height  of  their  development,  has  been  involved 
in  much  obscurity.  In  1900  Escherich  described 
a  fatal  hospital  epidemic  among  young  children 
in  which  he  observed  that  the  stools  in  certain 
instances  consisted  almost  wholly  of  Gram- 
positive  rods,  morphologically  of  the  type  just 
mentioned.  He  gave  to  this  condition  the  name 
of  blue  bacillosis  {Blaue  Bacillose)  to  signalize 
the  fact  of  the  Gram-positive  nature  of  the 
bacilli  in  question.  Escherich  also  observed 
that  when  the  bacterial  stools  of  the  children 
in  question  were  transferred  to  ordinary  culture 
media,  there  was  no  growth  of  Gram-positive 
organisms,  but  only  of  the  Gram-negative 
colon-like  bacteria  which  were  an  insig- 
nificant feature  in  the  field.     This  latter  observa- 


22  INFANTILISM 

tion  I  can  confirm,  and  it  is  only  by  tlie  use 
of  very  careful  cnltnral  methods  that  it  has 
been  possible  to  obtain  some  insight  into  the 
nature  of  the  Gram-positive  organisms  seen  in 
these  fields.  As  will  be  pointed  out  in  what 
follows,  there  are  three  kinds  of  organisms 
which  may  give  rise  to  appearances  in  the 
Gram-stained  field  similar  to  those  occasioned 
by  the  presence  of  the  Gram-positive,  slightly 
curved  or  straight  rods  which  have  been  men- 
tioned. These  organisms  are  the  Bacillus  hi- 
fidus  of  Tissier,  the  Bacillus  acidophilus  of 
Moro  and  a  hitherto  apparently  undescribed 
organism  which  will  be  called  here  Bacillus 
infantilis. 

That  the  B.  hifidus  of  Tissier,  or  an  organ- 
ism bearing  an  extremely  close  resemblance  to 
it,  is  present  in  large  numbers  in  the  intes- 
tinal contents  of  our  cases  of  infantilism  is 
indicated  in  part  by  the  study  of  the  sedi- 
ments of  the  sugar-bouillon  fermentation  tubes 
and  in  part  by  other  cultural  procedures.  I 
observed  several  years  ago  that  when  the  mixed 
fecal  flora  from  a  case  of  infantilism  or  from 
certain  instances  of  acute  or  subacute  enteritis 
in  infants  were  inoculated  into  sugar-bouillon 
fermentation  tubes  (lactose,  dextrose  and  saccha- 
rose) there  was  a  very  abundant  growth  in 
the  tubes  of  bifid  organisms,  either  growing 
separately    or   in    groups    in    which    individual 


INFANTILISM  23 

bifurcating  organisms  are  fused  together  so  as 
to  give  rise  to  varied  pictures.  A  study  of 
the  fermentation  tube  sediments  not  merely 
served  to  attract  attention  to  the  occurrence 
of  bifid  types  of  bacteria  in  the  intestinal  con- 
tents, but  also  drew  attention  to  certain  other 
forms  of  bifid  microorganisms  that  may  occur 
under  the  same  cultural  conditions  and  to  the 
importance  of  certain  coccal  forms  of  bacteria. 
It  will  be  convenient  to  discuss  the  dominant 
types  of  organisms  in  our  cases  under  the 
following  heads:  (1)  organisms  of  the  B.  hifidus 
type;  (2)  organisms  of  the  B,  infantilis  type; 
(3)    coccal  forms. 

(1)  Organisms  of  the  Bacillus  hifidus  Type. 
Although  it  has  been  easy  to  obtain  from  the 
fermentation  tubes  very  abundant  and  domi- 
nant growths  of  bifid,  lactic  acid-producing 
microorganisms  corresponding  to  the  morphology 
of  B.  hifidus  of  Tissier,  considerable  difficulty 
was  encountered  in  obtaining  these  organisms 
in  pure  culture.  Mr.  Kendall  has  now  succeeded 
in  growing  the  organisms  in  question  on  various 
media  under  anaerobic  conditions.  The  organ- 
isms were  derived  not  merely  from  the  stools 
of  patients  with  infantilism,  but  also  from  the 
stools  of  certain  cases  of  subacute  enteritis  in 
infants  which  have  already  been  alluded  to  as 
presenting  fields  made  up  almost  exclusively  of 
Gram-positive  bacilli.    The  organisms  in  ques- 


24  INFANTILISM 

tion  grow  on  dextrose-agar  plates  as  lenticular 
or  helmet- shaped  colonies  and  on  anaerobic 
agar  slants  present  beaded,  grey,  shining 
colonies  slightly  opaque  or  translucent.  Mor- 
phologically, the  organisms  present  the  typical 
Y-shaped  or  bifid  form.  They  are  Gram-posi- 
tive and  vary  in  size  from  two  to  four  microns 
in  length  and  from  six  tenths  of  a  micron  to 
one  micron  in  width.  They  are  sometimes 
apparently  slightly  motile.  In  fermentation 
tubes  and  associated  with  other  bacteria  they 
grow  well  in  dextrose,  lactose  and  saccahrose 
bouillon,  but  especially  well  in  the  two  former. 
They  produce  lactic  acid  and  are  capable  of 
maintaining  themselves  at  a  considerable  grade 
of  acidity.  For  this  reason  they  have  been 
classed  as  acidophile  bacteria.  The  justice  of 
regarding  them  as  strict  acidophile  organisms 
may,  however,  perhaps  be  questioned,  since  in 
the  absence  of  interfering  organisms  they  may 
grow  well  in  sugar-bouillon  in  which  the  acidity 
is  in  large  degree  neutralized  by  the  presence 
of  calcium  carbonate.  It  appears  rather  that 
they  are  capable  of  withstanding  a  higher  degree 
of  acidity  than  some  other  intestinal  micro- 
organisms, as,  for  example,  colon  bacilli,  and 
are  therefore  able  to  thrive  when  the  colon 
bacilli  are  no  longer  able  to  reproduce  them- 
selves in  consequence  of  the  excess  of  acid. 
These   organisms   coaggulate   milk,  but   do    not 


INFANTILISM  25 

peptonize  it.  They  do  not  grow  on  gelatin. 
Although  they  may  be  regarded  as  anaerobic 
organisms,  it  is  true  that  after  a  time  they 
grow  to  the  surface  in  agar  stick  cultures  and 
may  even  cause  a  slight  elevation  of  the  sur- 
face of  the  agar.  These  organisms  do  not 
always  show  bifurcation,  and  under  certain 
cultural  conditions  tend  to  develop  rarefication 
of  their  protoplasm  in  spots,  so  that  the  Gram- 
stain  is  retained  irregularly,  giving  rise  to 
punctate  forms  of  bifidus.  This  punctate  form 
of  bifidus  may  be  plain  or  may  undergo 
branching. 

Successful  plate  cultures  indicate  that  the 
bifidus  type  of  organisms  is  very  abundantly 
represented  in  the  feces  of  certain  cases  of 
intestinal  disorder,  including  not  only  cases  of 
infantilism,  but  the  subacute  conditions  already 
mentioned.  They  have  been  studied  by  Mr. 
Kendall  with  especial  care  in  Case  I  of  the 
infantilism  group  and  in  some  instances  of 
subacute  intestinal  infection  characterized  by 
Esche rich's  blue  bacillosis.  I  have  found  them 
also  in  Cases  II,  III  and  IV.  It  is  impossible 
at  present  to  say  just  how  large  a  proportion 
of  the  organisms  in  the  cases  mentioned  belong 
to  the  B.  bifidus  type,  but  the  plate  cultures 
indicate  that  they  are  prominent  all  the  time, 
though  sometimes  more  largely  dominant  than 
at   others.    With   the   exception   of   Case   I  of 


26  INFANTILISM 

our  group  of  infantilism  patients,  the  presence 
of  B,  hifidus  in  large  numbers  in  the  stools 
has  been  commonly  inferred  from  the  bifid 
forms  found  in  the  fermentation  tube  sedi- 
ments and  from  the  morphological  characters 
of  the  organisms  in  the  smears  from  the  stools, 
rather  than  from  cultures  on  plates. 

It  seems  worth  noting  that  in  the  studies 
made  from  mucus  obtained  from  the  stools  in 
Case  I,  Case  II  and  in  one  of  our  patients 
with  subacute  blue  bacillosis,  sugar-bouillon 
fermentation  tubes  inoculated  with  carefully 
washed  mucus  have  shown  the  development  of 
a  great  abundance  of  bifid  forms,  apparently 
in  almost  pure  culture,  whereas  inoculations 
made  from  the  fecal  material  from  the  same 
cases  showed  a  far  less  rich  growth  as  well 
as  the  presence  of  other  varieties  of  micro- 
organisms. 

(2)  Organisms  of  the  Bacillus  Infantilis  Type, 
The  organism  to  which  the  name  Bacillus 
infantilis  has  been  applied  was  first  noticed  by 
Mr.  Kendall  while  working  on  the  cases  of 
infantilism  described  in  this  paper.  This 
organism,  or  type  of  organism — for  there  are 
several  variants — occurs  not  rarely  in  the  stools 
of  breast-fed  and  bottle-fed  infants.  It  has 
been  isolated  also  from  a  number  of  children 
ranging  from  two  to  seven  years  of  age,  and 
has    been     obtained     from    one     adult.    Under 


INFANTILISM  27 

normal  conditions  the  number  of  organisms  of 
this  type  growing  upon  nutrient  sugar-agar 
plates  is  not  great.  In  fact  it  is  frequently- 
difficult  to  obtain  cultures.  In  certain  cases, 
however,  especially  in  those  showing  the  Gram- 
positive  fields  of  the  blue  bacillo sis  type,  the 
number  is  greatly  increased,  judging  from  their 
abundance  in  plate  cultures. 

In  stained  stools,  the  organisms  appear  as 
rather  thin.  Gram-positive  rods,  agreeing  in 
size  with  Tissier's  B,  hifidus  communis.  The 
B.  infantilis  has  not  been  observed  to  occur 
with  pointed  ends,  as  is  the  case  with  at  least 
some  varieties  of  the  B,  hifidus.  The  organism 
forms  spores  which  are  central  (but  occasion- 
ally terminal),  causing  a  slight  swelling  of  the 
rod.  In  the  vegetative  state  B.  infantilis  as 
studied  by  Mr.  Kendall  is  actively  motile.  It 
usually  occurs  singly  or  in  pairs,  but  under 
certain  conditions,  particularly  in  fluid  media, 
may  form  chains  of  several  elements.  (In  length 
it  varies  from  2.5 — 3  microns,  in  width  from 
0.5 — 0.75  microns.)  Occasionally  one  sees  dis- 
tinct branches  in  anaerobic  dextrose  agar.  B. 
infantilis  is  ordinarily  isolated  from  anaerobic 
plates,  although  it  has  been  obtained  without 
difficulty  in  some  instances  when  grown  under 
aerobic  conditions.  After  the  first  generation 
upon  artificial  media,  it  grows  readily  in  the 
incubator   at   body  temperature   and  much  less 


28  INFANTILISM 

readily  at  20°  C.  The  submerged  colonies  are 
of  two  types,  one  lenticular  and  yellowish,  the 
other  rather  irregular  in  outline  and  woolly 
in  appearance.  The  surface  colonies  are  usually 
dull  and  have  a  tendency  to  spread.  The  sur- 
face growths  are  gray.  There  are  two  types 
of  growth  upon  agar.  The  first  is  almost 
invisible  and  is  limited  largely  to  the  conden- 
sation water.  The  second  is  more  vigorous 
and  spreading.  Spores  are  readily  formed  upon 
the  surface  of  slants,  usually  within  48  hours. 
The  bacilli  in  the  spore  stage  are  slightly 
spindle-shaped,  frequently  with  a  deeply  stain- 
ing Gram-positive  granule  at  either  end  of  the 
rod,  more  usually  at  one  end  only.  Many  cul- 
tures produce  a  mucin-like  substance.  In  fluid 
media  spore-formation  is  delayed  and  is  fre- 
quently absent.  In  sugar-bouillon  (dextrose, 
lactose)  there  are  two  types  of  growth.  The 
first  corresponds  to  the  form  that  grows  poorly 
on  agar,  showing  a  slight  sediment  with  usually 
a  transient  turbidity  and  no  pellicle;  the  sec- 
ond type  of  growth  is  indicated  by  a  moderate 
turbidity  and  the  development  of  a  sediment 
and  usually  a  pellicle.  Upon  plain  broth  there 
is  no  turbidity  and  in  many  strains  a  pellicle 
is  formed.  The  bacilli  from  the  sediment  are 
usually  elongated,  show  irregular  or  punctate 
staining  and  may  occur  singly,  in  pairs  or 
less   commonly   in   chains.     Milk   is  not   coagu- 


INFANTILISM  29 

lated  by  B.  infantilis,  nor  is  there  any  evi- 
dence of  peptonization.  The  reaction  is  usually 
slightly  alkaline  after  four  to  seven  days, 
although  this  alkalescence  is  not  marked  and 
may  be  absent.  In  fermentation  tubes  the 
organisms  produce  acid,  but  no  gas  in  dextrose 
or  lactose  or  saccharose.  The  acid  production 
in  lactose  is  relatively  slight.  On  gelatin  there 
is  a  very  slight  growth  and  frequently  none 
at  all.  There  is  no  liquefaction.  B,  infantilis 
inhibits  the  gas  production  of  the  colon  bacillus 
when  the  two  organisms  are  grown  in  dex- 
trose or  lactose  bouillon,  the  gas  production  of 
the  colon  bacillus  being  sometimes  restricted 
to  the  extent  of  80  per  cent.  The  colon  bacilli 
grow  at  first  more  rapidly,  but  soon  the  advan- 
tage thus  obtained  is  permanently  lost  and 
B.  infantilis  distinctly  checks  the  further  growth 
of  B,  coli,  B,  infantilis  forms  neither  indol 
nor  skatoL  It  forms  volatile  bases  in  great 
abundance,  chiefly  ammonia.  We  have  found 
methylamin  among  the  products. 

It  is  impossible  to  state  at  present  to  what 
extent  the  Gram-positive  rods  observed  in  the 
fields  obtained  from  children  with  infantilism 
consist  of  B.  infantilis. 

(3)  Coccal  Forms,  The  third  group  of  organ- 
isms consists  of  coccal  forms,  the  relation  of 
which  to  one  another  is  still  obscure.  In  our 
cases  of  infantilism,  Griam-positive  coccal  forms 


30  INFANTILISM 

have  at  times  been  abundant,  and  even  when 
not  prominent  in  the  fecal  fields  may  grow  freely 
in  the  sngar-bonillon  fermentation  tubes.  They 
consist  chiefly  of  larger  and  smaller  diplococci 
or  coccobacilli  corresponding  closely  in  mor- 
phology and  cultural  characters  to  the  entero- 
coccus  of  Thiercelin  or  the  Micrococcus  ovalis 
described  by  Hirsch-Libmann.  The  enterococcus 
forms  acid  on  dextrose,  lactose  and  saccharose 
and   coagulates   milk. 

In  one  of  our  cases  of  infantilism  associated 
with  profound  anaemia  (Case  V)  the  fecal 
fields  showed  very  large  numbers  of  small. 
Gram-positive  cocci.  These  were  found  espe- 
cially in  certain  parts  of  the  stools  where  they 
were  seen  to  the  exclusion  of  other  organisms. 
It  was  especially  in  the  mucus  and  about  the 
epithelial  elements  that  these  organisms  were 
noted  in  such  abundance  and  concentration. 
In  respect  to  these  organisms  Case  V  presents 
an  exception  to  the  remaining  four  cases  in 
the  infantilism  group.  The  character  of  the 
coccal  forms  occuring  in  this  case  have  not  as 
yet  been   thoroughly   studied. 

It  is  worthy  of  mention  that  neither  the 
B.  hifidus  forms  nor  the  B.  infantilis  forms 
that  have  been  isolated  from  our  cases  of 
infantilism  have  exhibited  pathogenicity  when 
injected  into  guinea-pigs.  In  Case  I  it  was 
observed  that  the  relative  proportion  of  organ- 


INFANTILISM  31 

isms  of  these  three  types  which  appeared  upon 
anaerobic  plates  varied  a  good  deal  from  day 
to   day  without   apparent   cause. 

As  regards  the  presence  of  organisms  of  the 
B,  coll  and  B.  lactis  aerogenes  groups,  it  may 
be  stated  that  such  organisms  are  infrequent 
in  the  feces  in  our  cases  of  infantilism,  when 
they  are  in  their  most  pronounced  stage.  This 
is  true  also  of  the  subacute  cases  of  intestinal 
infection  already  mentioned.  Indeed  in  this 
latter  group  of  cases  it  is  the  rule  to  see  Gram- 
positive  fields,  wholly  free  from  organisms, 
suggesting  either  B.  lactis  aerogenes  or  B.  coli. 
It  is  probably  owing  to  the  almost  entire  or 
the  complete  absence  of  these  normal  intes- 
tinal inhabitants  that  the  gas  production  in 
the  fermentation  tubes  inoculated  with  the 
mixed  fecal  flora  from  the  cases  of  infantilism 
at  their  height,  has  been  slight  or  lacking. 
These  conditions,  however,  hold  true  only  for 
our  cases  in  their  most  highly  developed  form. 
As  recovery  has  set  in  it  has  been  observed  in 
Cases  I,  II,  III  and  IV  that  with  improvement 
in  nutrition  there  has  been  a  relative  decrease 
in  the  number  of  Gram-positive  bacterial  ele- 
ments in  the  feces  and  a  corresponding  develop- 
ment of  Gram-negative  forms  corresponding  to 
B.  lactis  aerogenes  and  B.  coli.  In  the  case 
of  infantilism  (Case  II)  in  which  the  greatest 
improvement    in    nutrition    has    been    observed, 


32  INFANTILISM 

B.  lactis  aerogenes  lias  lately  been  isolated 
from  the  plates  in  great  numbers.  In  this 
case  an  increase  in  gas  production  has  gone 
hand  in  hand  with  the  establishment  of  the 
normal  flora  in  the  feces.  It  may  also  be 
remarked  that  in  this  case  the  improvement  in 
nutrition  and  the  gradual  restoration  of  the 
normal  flora  occurred  with  comparative  rapidity 
during  a  period  of  eighteen  months,  and  not 
until  after  the  child  had  reached  the  age  of 
eight  years;  previous  to  this  recovery  had 
been  extremely  slow  during  three  years.  It 
should  also  be  stated  that  in  this  same  case 
(Case  II)  the  disappearance  of  Gram-positive 
organisms  of  the  B,  hifidus  type  was  associated 
with  the  great  falling  off  in  the  growth  of 
B.  hifidus  in  the  fermentation  tubes.  B.  hifidus 
was  represented  in  the  fermentation  tubes  not 
by  well-staining  bifid  forms,  but  by  small 
punctate  rod  forms  apparently  atrophic  in 
character,  though  still  capable  of  cultivation. 
Finally  it  should  be  stated  in  reference  to 
Case  II  that  with  the  disappearance  of  organ- 
isms of  the  B,  hifidus  type  and  the  reestab- 
lishment  of  B,  lactis  aerogenes  and  B.  coli,  the 
intestinal  tract  began  to  show  excessively  large 
numbers  of  B,  aerogenes  capsulatus.  This 
organism  had  not  before  been  noted  as  a 
prominent  inhabitant  of  the  intestinal  tract, 
and  was  indeed  probably  present  in  only  small 


INFANTILISM  33 

numbers,  if  at  all,  previous  to  the  eighth  year 
of  life. 

The    Ueinaky    Expressions    of    the    Ineection 
underlying    infantilism 

Considerable  attention  was  devoted  to  the 
characters  of  the  urine  in  our  cases  of  infan- 
tilism, especially  in  Cases  I,  II  and  III.  In 
Case  I  the  specific  gravity  of  the  urine  ranged 
from  1010  to  1015,  and  the  volume  of  urine 
was  habitually  large — 800  c.c.  to  1100  c.c.  In 
Case  II,  during  the  time  between  the  fifth  and 
ninth  years  of  life,  the  specific  gravity  of  the 
urine  ranged  usually  from  1010  to  1018.  The 
volume  of  urine  varied  from  600  c.c.  to  1000 
c.c.  daily.  In  Case  III  the  volume  was  mod- 
erate and  the  specific  gravity  ranged  from 
1020  to  1030.  In  the  remaining  cases  there 
were  not  enough  observations  to  enable  any 
general  statements  to  be  made  as  to  the  vol- 
ume and  specific  gravity  of  the  urine. 

The  nitrogen  excretion  was  recorded  in  three 
instances,  and  it  may  be  stated  that  it  tends 
to  be  high  in  proportion  to  the  weight  of  the 
child.  For  example,  in  Case  II,  with  a  weight 
of  32  pounds,  the  nitrogen  excretion  ranged 
from  5.7  grams  to  6.5  grams  daily.  In  Case  I 
the  nitrogen  excretion  ran  uncommonly  high, 
namely  from  7  to  9  grams  daily  at  a  time 
when  the   weight   was   only  25   pounds.     These 


34  INFANTILISM 

results  are  clearly  attributable  to  the  high 
protein  feeding  which  was  incidental  to  efforts 
to  reduce  the  carbohydrates,  which  had  proved 
very  liable  to  cause  diarrhoea.  The  excessive 
appetite  was  doubtless  a  factor  in  rendering 
it  easy  to  consume  so  large  an  amount  of 
protein  food.  The  same  statement  may  be 
made,  though  less  strongly,  in  regard  to  Case 
II.  In  Case  III  the  nitrogen  excretion  cannot 
be  said  to  have  run  abnormally  high  in  pro- 
portion to  the  weight  of  the  child,  though  full 
data  relating  to  this  point  are  not  available. 

In  regard  to  the  nitrogen  of  ammonia  in  our 
cases,  there  is  nothing  noteworthy.  In  Case  III 
the  nitrogen  of  ammonia  formed  from  2.4  to 
3.3  per  cent,  of  the  total  nitrogen  excreted. 
In  Case  II  the  nitrogen  excretion  was  likewise 
normal,  seldom  going  above  4  per  cent,  of  the 
total  nitrogen.  In  Case  I  also  the  nitrogen  of 
ammonia  usually  varied  within  normal  limits. 
A  very  large  number  of  observations  in  this 
case  show  that  the  percentage  of  nitrogen  of 
ammonia  varied  habitually  between  3.25  and 
4.50  per  cent.  At  one  time,  while  the  patient 
had  a  cold  in  the  head,  the  nitrogen  of  ammonia 
rose  on  two  successive  days  to  4.78  and  5.96 
per  cent,  of  the  total  nitrogen.  The  urine  at 
this  time  gave  a  strong  Legal  reaction  for 
acetone  in  the  distillate.  On  a  few  other  occa- 
sions, however,  the  nitrogen  of  ammonia  reached 


INFANTILISM  35 

or    exceeded   these   figures   without   being    asso- 
ciated  with   acetone. 

As  regards  the  excretion  of  uric  acid  in  this 
case,  it  may  be  stated  to  have  been  so  variable, 
as  measured  by  the  ratio  between  uric  acid 
and  the  urea  output,  that  no  definite  con- 
clusions can  be  reached  in  the  case  of  patients 
Nos.  II  and  III.  This  is  true  also  of  Case  I 
during  the  early  period  of  observation,  but 
during  recent  months  (March  and  April,  1908), 
under  conditions  of  great  uniformity  of  diet 
and  habits,  the  uric  acid  excretion  (like  that 
of  total  nitrogen)  varied  but  little  from  day 
to  day  With  a  few  exceptions  the  uric  acid 
bore  a  proportion  to  the  urea  very  close  to 
1:30.  Taking  into  account  the  nature  of  the 
diet^  this  must  be  regarded  as  indicating  an 
excessive  excretion  of  uric  acid,  both  absolute 
and  relative.^  It  is  worthy  of  notice  that  there 
should  have  occurred  a  rise  both  in  the  abso- 
lute and  the  relative  amount  of  uric  acid 
excreted  just  at  the  time  when  the  nutritional 
conditions  of  the  patient  began  to  undergo  a 
distinct   improvement. 

*  Given  in  section  on  therapeutic  measures. 

'For  example  the  actual  quantities  excreted  during  successive 
days  is  expressed  in  grams  by  the  following  figures:  0.383,  0,388, 
0.413,  0.454,  0.397,  0.387,  0.439,  0.406,  0.421,  0.427,  0.399,  0.488, 
0.458,  0.486,  0.452,  0.449,  0.477,  0.433,  0.443,  0.517,  0.463,  0.427, 
0.432,  0.449,  0.459,  0.480,  0.471,  0.545,  0.452,  0.473,  0.461,  0.468, 
0.466,  0.456,  0.406,  0.415,  0.467,  0.422,  0.420,  0.397,  0.437. 


36  INFANTILISM 

Special  attention  was  devoted  to  a  study  of 
the  urinary  indications  of  putrefactive  decom- 
position in  the  intestine.  Such  indications  are 
known  to  have  been  very  pronounced  in  Cases 
I,  II,  III  and  IV,  and  very  similar  indications 
of  putrefaction  have  been  found  in  the  sub- 
acute infections  of  early  infancy  already  alluded 
to  as  being  associated  with  the  Gram-positive 
fecal  fields.  The  urinary  signs  of  excessive 
decomposition  in  the  intestine  are  shown  mainly 
in  four  different  ways:  First,  there  is  a  rise 
in  the  ethereal  sulphates.  It  is  no  uncommon 
thing  in  cases  of  infantilism  for  the  ratio  of 
the  ethereal  to  the  preformed  sulphates  to 
reach  1:4  or  1:6,  whereas  the  normal  ratio  in 
childhood  is  1:12  to  1:18.  Even  higher  pro- 
portions are  observed  in  the  subacute  stage 
which  the  writer  regards  as  leading  into  the 
chronic  state  of  infantilism.  Secondly,  pro- 
nounced indicanuria  is  a  very  prominent  fea- 
ture, as  shown  in  all  the  cases  examined  except 
Case  V,  which  did  not  come  under  close 
observation  until  the  nutritional  state  had  begun 
to  improve.  Quantitative  determinations  of  the 
indican  have  not  been  made,  but  the  qualitative 
results  leave  little  doubt  that  the  indican  is 
habitually  highly  excessive  when  the  disease  is 
at  its  height.  This  is  true  also  of  the  sub- 
acute fore-period  of  the  disease.  It  is  true, 
however,  that  with  the  improved  intestinal  con- 


INFANTILISM  37 

ditions  which  precede  a  change  for  the  better 
in  nutrition,  the  indican  may  begin  to  decline. 
There  may  thus  be  a  time  in  the  history  of 
the  disease  when  despite  the  fact  that  the 
child  still  remains  nearly  stationary  in  weight 
from  week  to  week,  and  even  from  month  to 
month,  the  indican  is  much  lower  than  was 
previously  the  case.  Another  apparently  regu- 
lar feature  of  the  putrefactive  decompositions 
in  infantilism  is  the  occurrence  of  an  excess  of 
phenol  in  the  distillate  of  the  urine  (the  dis- 
tillates include  phenols  and  cresols).  The  ob- 
servations made  in  our  cases  are  partly  quan- 
titative by  the  method  of  Kossel  and  Penny 
and  partly  qualitative  (with  Millon's  reagent). 
In  Case  II  the  repeated  examinations  of  the 
distillate  made  at  short  intervals  during  a 
period  of  five  years  showed  an  excess  of  phenol 
to  be  a  regular  feature.  The  phenol  for  24 
hours  varied  from  38-90  milligrams  (in  the 
quantitative  observations).  Case  III  likewise 
gave  very  strong  MUon  reactions  with  the  dis- 
tillate. In  Case  I  the  distillate  also  regularly 
contained  excessive  amounts  of  phenolic  sub- 
stances as  indicated  by  the  following  figures 
(representing  milligrams)  for  the  twenty-four 
hours:  75,  71,  84,  79,  87,  93,  62,  78,  90,  100, 
74,  62,  87,  90,  73,  90,  45,  81,  91,  63,  74.  Once 
without  assignable  cause  the  phenol  in  the  dis- 
tillate   fell    to  19    milligrams.     Another   feature 


38  INFANTILISM 

of  tlie  urine  referable  to  putrefactive  decom- 
position in  tlie  intestine  is  the  presence  of 
aromatic  oxyacids  in  the  urine.  It  is  probable 
that  both  paraoxyphenylacetic  acid  and  para- 
oxyphenylpropionic  acid  are  frequently  present 
in  excess  in  these  cases.^  The  acids  in  solu- 
tion in  the  urine  are  capable  of  reacting  with 
Millon's  reagent  even  in  the  cold,  and  it  is 
a  noteworthy  feature  of  our  cases  that  in  many 
instances  the  urine  gives  the  characteristic 
behavior  of  the  aromatic  oxyacids  when  treated 
with  Millon's  reagent  in  the  cold.  Urines  con- 
taining these  aromatic  oxyacids  also  give  a 
marked  diazo-reaction  after  distillation  of  the 
phenols.  It  may  be  mentioned  further  that 
the  urines  from  the  subacute  infections,  which 
are  regarded  as  constituting  the  early  stage  of 
chronic  infantilism,  are  liable  to  give  a  very 
pronounced  reaction  with  Millon's  reagent  in 
the  cold  in  the  absence  of  volatile  phenols. 
Finally  it  should  not  be  overlooked  that  a 
marked  degree  of  indolaceturia  occurred  in 
Case  I  and  was  a  continuous  feature  in  this 
patient.  The  presence  of  indolacetic  acid  was 
detectable  also  in  the  urine  of  Case  11  where, 
however,  it  was  not  pronounced.     In  Case  III 

'Paraoxyphenylacetic  acid  is  not  readily  burned  in  the  body 
and  hence  appears  in  the  urine  when  absorbed  from  the  intestine. 
The  homologous  higher  acid  undergoes  combustion  and  hence  is 
less  likely  to  reach  the  urine,  even  if  formed  in  equal  or  greater 
amount  as  the  result  of  putrefaction. 


INFANTILISM  39 

it  gave  rise  to  a  moderate  reaction  with  strong 
hydrochloric  acid  and  potassium  nitrite.  From 
experience  gained  with  the  urines  of  the  sub- 
acute infections  leading  to  chronic  infantilism, 
I  am  disposed  to  think  that  indolaceturia  is 
not  a  regular  feature  in  this  type  of  disease, 
although  it  is   sometimes  very  prominent. 

It  may  be  further  stated  that  the  urines 
from  the  cases  of  infantilism  showed  slight  or 
negative  reactions  with  paradimethylamidoben- 
zaldehyde,  that  skatol  red  was  regularly  absent 
and  that  in  Cases  I,  II  and  III  the  urines 
were  sometimes  observed  to  show  a  slight 
reducing  action  when  boiled  with  Fehling's 
solution. 

Features  Relating  to  the  Intestinal  Contents. 
There  are  several  features  relating  to  the 
gross  and  microscopical  appearances  of  the 
intestinal  contents  and  to  their  chemical  nature 
which  require  at  least  brief  consideration.  The 
character  of  the  movements  is  influenced  to  a 
considerable  extent  by  the  nature  of  the  food, 
and  in  general  it  may  be  stated  that  on  an 
ordinary  mixed  diet  containing  a  fair  propor- 
tion of  fat,  carbohydrates  and  proteins  and  in 
which  milk  forms  part  of  the  regimen,  the 
movements  are  voluminous,  gray  or  light-brown 
in  color  and  of  sufficiently  low  specific  gravity 
to  float  on  the  surface  of  water.  If  the  quan- 
tity of  food  be  considerable  the  movements  may 


40  INFANTILISM 

be  very  large  indeed.  If  the  carboliydrates  be 
abundant,  tbe  fresh  movements  are  apt  to  be 
filled  with  bubbles  of  gas.  The  stools  are 
usualy  formed,  though  so  soft  that  any  increase 
in  the  watery  constituents  gives  the  stool  a 
diarrhoeal  character.  The  movements  usually 
have  a  sour  odor  which  is  clearly  recognizable 
despite  the  fecal  odor  due  to  the  presence  of 
indol.  The  odor  of  butyric  acid  is  seldom 
more  than  slight  and  is  frequently  absent. 
Mucus  is  very  abundant  at  times  both  in, 
masses  on  the  surface  of  the  feces  and  inti- 
mately mingled  with  them  in  small  bits.  In 
loose  movements  after  the  use  of  calomel  large 
flakes  of  mucus  are  usually  brought  away. 
Large  numbers  of  well-preserved  individual 
epithelial  elements  are  habitually  carried  away 
in  the  feces.  Their  number  may  be  very  large 
in  some  parts  of  the  stool.  Preparations  of 
the  feces  show  moderately  dense  bacterial 
fields  almost  always  containing  numerous  epi- 
thelial elements,  with  nuclei  usually  well  pre- 
served and  with  a  small  area  of  cytoplasm 
about  them.  These  epithelial  elements  may 
occur  separated  or  closely  aggregated  in  con- 
siderable numbers.  In  some  cases  it  is  com- 
mon to  find  on  the  surface  of  the  feces  and 
mingled  with  the  mucus,  numbers  of  small, 
spheroidal  cells,  from  three  to  four  microns  in 
diameter,   containing   spherical  nuclei   and   pos- 


INFANTILISM  41 

sessing  homogeneous,  highly  refractile  cell 
bodies.  They  are  often  bile-stained,  and  if 
present  in  large  numbers  give  a  pink  or  red- 
dish color  to  the  mucus  with  which  they  are 
mixed.  These  cell  elements  stain  readily  with 
carbol-fuchsin  and  are  acid-fast.  When  I  first 
saw  them  I  thought  they  might  be  epithelial 
elements^  but  now  believe  them  to  have  an 
origin  extraneous  to  the  digestive  tract.  They 
may  possibly  be  some  form  of  yeast,  but  the 
fact  that  we  have  not  been  able  to  grow  them 
in  sugar  media  appears  against  this  view. 

The  microscopical  fields  show  the  presence 
of  an  abundance  of  fatty  acid  crystals,  and  it 
is  owing  to  the  presence  of  these  that  watery 
suspensions  of  feces  (say  one  gram  feces  to 
ten  grams  water)  in  a  test  tube  show  the 
optical  peculiarities  due  to  the  presence  of 
large  nujnbers  of  small  crystals.  The  reaction 
of  the  feces  is  usually  slightly  acid,  but  often 
it  is  neutral.  If,  however,  meat  be  an  abun- 
dant constituent  of  the  diet  the  reaction  may 
be  sliglitly  alkaline.  In  some  instances  it  has 
been  noticed  that  the  drying  of  the  feces  is 
associated  with  the  separation  of  large  num- 
bers of  crystals  which  have  the  characteristic 
appearance  of  triple  phosphates  (ammonio- 
magnesian  phosphate). 

There  are  also  several  chemical  characters 
in  the  feces  of  infantilism  which  deserve  men- 


42  INFANTILISM 

tion.  Even  when  the  feces  are  acholic  in 
appearance,  extraction  with  alcohol  shows  the 
presence  of  moderate  quantities  of  bilirubin. 
It  is  thus  erroneous  to  draw  the  conclusion 
from  the  appearance  of  the  stools  that  bile 
fails  to  enter  the  intestinal  tract.  It  is  also 
noteworthy  that  the  reaction  for  hydrobilirubin 
with  concentrated  bichloride  of  mercury  is 
extremely  slight  and  sometimes  negative.  This 
points  to  the  absence  of  a  strong  reducing  action 
on  the  part  of  the  bacteria  present  in  the 
intestinal  tract.  I  think  it  probable  that  the 
failure  to  detect  marked  evidence  of  reducing 
action  by  the  bacteria  in  the  digestive  tract 
is  to  be  explained  in  these  cases  by  the  com- 
paratively small  number  of  microorganisms  of 
the  butyric  acid  type — a  type  conspicuously 
active  in  causing  reductions.  Indol  is  a  nearly 
constant  constituent  of  the  freshly  voided  feces 
in  children  suffering  from  intestinal  infanti- 
lism. It  may  easily  be  demonstrated  in  the 
distillate  either  by  the  paradimethylamidoben- 
zaldehyde  reaction  of  Ehrlich,  or  better  still, 
by  means  of  the  /8-naphthaquinone  sodium 
monosulphonate  reaction.  The  quantity  is  usually 
not  large,  but  rarely  may  run  up  to  20-30 
milligrams  in  100  grams  of  the  moist  feces. 
The  presence  of  indol  in  the  feces  may  be 
correlated  with  the  occurrence  of  strong  indi- 
canuria,  but  sometimes  the  indicanuria  may  be 


INFANTILISM  ,      43 

pronounced  even  though  only  a  trace  of  indol 
is  detectable  in  the  feces.  This  is  owing  to 
the  fact  that  there  is  not  any  fixed  relation 
between  the  quantity  of  indol  produced  in  the 
intestine  and  the  quantity  absorbed.  As  the 
patients  improve  in  digestion  and  nutrition, 
the  quantity  of  indol  in  the  feces  grows  less, 
and  may  in  time  become  very  slight.  In 
diarrhoeal  movements  also  the  proportion  of 
indol  is  apt  to  be  slight.  I  have  never 
observed  skatol  in  the  movements  from  any 
patients  of  the  type  now  under  consideration. 
Phenolic  substances  can  almost  always  be 
detected  in  slight  amounts  in  the  distillate 
from  the  feces.  Sometimes  the  reaction  for 
them  is  strong.  In  Case  I  the  feces  contained 
a  substance  which  gave  reactions  correspond- 
ing to  indolacetic  acid.  I  have  not,  however, 
had  the  opportunity  to  separate  this  substance 
in  purity  and  in  sufficient  quantity  from  the 
feces  to  actually  settle  its  identity.  The  hy- 
drogen sulphide  contents  of  the  feces  in  cases 
of    intestinal    infantilism    is    commonly    small.^ 

^  The    following    determinations    of   hydrogen    sulphide    in    the 
feces  are  indicative  of  the  range  in  percentage: 

Case  I                                                         Per  cent.  Per  cent. 

Date                                                            solids  H2S 

Nov.  27,  '07 25.89  .0144 

Nov.  29,  '07 9.97  .0144 

Dec.     3,  '07 29.85  .0113 

Dee.     5,  '07 25.41  .0127 


44  INFANTILISM 

The  hydrogen  sulphide  exists  in  bound  form, 
and  I  have  never  been  able  to  detect  the  free 
gas  in  the  fresh  movements.  Methyl  mercap- 
tan  is  also  absent  although  the  bacteria  from 
the  feces  may  produce  a  small  amount  of 
methyl  mercaptan  when  grown  in  plain  broth. 
It  appears  true  in  general,  however,  that  the 
bacteria  present  in  these  cases  do  not  form 
mercaptan  abundantly,  and  commonly  they  do 
not  make  it  at  all  under  the  conditions  just 
mentioned.  The  volatile  fatty  acids  derivable 
from  the  feces  in  cases  of  infantilism  are 
moderate  in  amount  and  appear  to  be  rather 
low  in  butyric  acid.  Acetic  acid  may  be 
detectable.  Aldehydes  have  not  been  detected. 
The  gas  production  of  the  mixed  fecal  flora 
when  grown  in  dextrose,  saccharose  and  lactose 
bouillon,  is  variable.  Commonly  it  is  smaller 
than  normal.  The  fecal  flora  may,  indeed,  fail 
to    form    gas    under    these    conditions.     With 

Per  cent.  Per  cent, 

solids  HsS 

'07 17.37  .041 

'07 32.60  .031 

'07 27.67 

'07 28.82  .0111 

'07 28.04 

'07 27.00  .0190 

'07 20.88  .0170 

'07 26.15  .0201 

'08 21.00  .009 

These  low  percentages  of  hydrogen  sulphide  are  the  more  note- 
worthy in  view  of  the  excess  of  other  putrefactive  products. 


Date 

Dec. 

7,    ' 

Dec. 

7,    ' 

Dec. 

10,    ' 

Dec. 

11,    ' 

Dec. 

14,    ' 

Dec. 

16,    ' 

Dec. 

20,    '( 

Dee. 

24,    '( 

Jan 

18,    '( 

INFANTILISM  45 

improvement  attended  by  a  return  of  B.  coli 
and  B.  lactis  aerogenes  the  gas  production 
increases   to    normal. 

The  Calcium  and  Magnesium  Balances,  In 
the  state  of  arrested  development  which  con- 
stitutes the  striking  feature  of  the  cases  of 
infantilism  here  reported,  it  is  of  especial 
interest  to  seek  for  information  regarding  the 
calcium  and  magnesium  intake  and  output.  It 
is  obvious  that  the  failure  of  skeletal  growth 
calls  for  explanation  and  that  this  explanation 
is  to  be  sought  either  in  the  inability  of  the 
skeleton  to  utilize  calcium  and  magnesium  com- 
ing to  it  in  the  blood,  or  the  inability  of  the 
blood  and  lymph  streams  to  obtain  from  the 
digestive  tract  sufficient  quantities  of  the  alkali 
earths  to  supply  the  necessary  materials  for 
skeletal  growth.  In  order  to  determine  the 
relations  between  the  intake  and  the  outgo  of 
the  alkali  earths  from  the  body  in  a  state  of 
infantilism,  two  observations  were  made  by 
Dr.  Wakeman  upon  Case  I,  each  observation 
covering  a  period  of  ten  days.  The  second  of 
these  observations  serves  as  the  basis  for  the 
data  to  be  referred  to  here,  the  observation 
having  been  made  under  thoroughly  satisfac- 
tory conditions  from  every  point  of  view.  The 
period  of  ten  days  in  question  extended  from 
noon,  March  10,  1908,  to  noon,  March  20,  1908 
— a  period  during  which  the  subject  remained 


46  INFANTILISM 

essentially  stationary  in  weight.  The  calcium, 
magnesium  and  phosphoric  acids  taken  in  the 
food  were  accurately  determined.  The  calcium, 
magnesium  and  phosphoric  acids  were  also 
determined  in  the  urine  and  feces  correspond- 
ing to  this  period,  the  feces  being  carefully 
marked  off  from  the  fore  and  after  periods  by 
means  of  charcoal. 

During  the  period  of  ten  days  the  calcium 
(calculated  as  calcium  oxide)  found  in  the 
urine  was  0.1151  grams,  giving  a  daily  average 
of  0.0115  grams.  In  the  feces  during  the  same 
period,  the  calcium  oxide  amounted  to  9.59  grams, 
giving  a  daily  average  of  0.959  grams.  The 
calcium  oxide  present  in  the  feces  and  urine 
together  during  the  ten  days  amounted  to 
9.71  grams,  with  a  daily  average  of  0.971 
grams.  The  calcium  oxide  of  the  food  during 
the  same  period  amounted  to  9.81  grams  with 
a  daily  average  of  0.982  grams.  There  was 
thus  a  positive  balance  of  calcium  during  the 
ten-day  period  amounting  to  100  milligrams,  in- 
dicating a  daily  retention  of  calcium  oxide  of 
only  10  milligrams.  It  is  roughly  estimated 
that  in  the  normal  growth  of  a  child  between 
the  second  and  the  sixteenth  years,  the  daily 
retention  of  calcium  oxide  by  the  body  should 
be  more  than  ten  times  the  amount  retained  in 
this  case.  The  amount  indicated  as  retained 
is,  in  fact,  so  small  in  this  instance  as  to  fall 


INFANTILISM  47 

almost  within  the  limit  of  experimental  error. 
There  was  thus  no  appreciable  retention  of 
calcium  oxide  during  the  period  in  question. 
During  another  ten-day  period  in  which  the 
calcium  oxide  was  studied  by  Dr.  Wakeman 
under  somewhat  less  favorable  experimental 
conditions,  there  was  shown  an  actual  loss  of 
calcium  oxide  in  the  feces  and  urine  as  com- 
pared with  the  calcium  oxide  taken  in  with 
the  food.  The  very  small  quantities  of  calcium 
found  in  the  urine  in  the  experimental  periods 
relating  to  this  case  point  to  defective  absorp- 
tion of  calcium  from  the  intestinal  tract. 

Precisely  similar  results  were  obtained  from 
the  study  of  the  magnesium  balance.  During 
the  ten -day  period  corresponding  to  the  one 
for  which  the  figures  for  calcium  oxide  have 
just  been  given,  the  urine  contained  one  gram 
of  magnesium  (calculated  as  magnesium  oxide), 
giving  an  average  of  0.10  grams  daily.  Dur- 
ing the  same  period  the  magnesium  in  the 
feces  was  equivalent  to  1.35  grams  of  mag- 
nesium oxide,  giving  an  average  of  0.135  grams 
daily.  The  magnesium  oxide  of  the  urine  and 
the  feces  in  this  ten-day  period  was  equivalent 
to  2.35  grams.  On  the  other  hand,  the  mag- 
nesium of  the  food  (calculated  as  magnesium 
oxide)  was  2.19  grams.  It  is  thus  evident 
that  for  the  entire  period  of  ten  days  there 
was  a  loss  of  magnesium  oxide  equivalent  to 


48  INFANTILISM 

0.16  grams.  This  amoimt  may  possibly  fall 
within  the  limits  of  experimental  error.  The 
result  indicates  that  during  the  period  in  ques- 
tion the  body  was  retaining  no  magnesium. 
The  cause  of  this  failure  of  the  organism  to 
retain  magnesium  and  calcium  will  be  discussed 
in  considering  the  pathology  of  infantilism. 

The  study  of  the  phosphoric  acid  of  the 
urine  and  feces  on  the  one  hand,  and  of  the 
food  on  the  other,  gives  results  comparable  with 
those  just  given  for  calcium  and  magnesium. 
During  the  ten-day  period  the  urine  contained 
10.46  grams  of  phosphoric  acid,  or  an  average 
of  1.05  grams  of  phosphoric  acid  daily.  The 
feces  during  the  same  period  contained  10.70 
grams  of  phos]ohoric  acid,  an  average  of  1.07 
grams  daily.  During  the  ten-day  period  the 
urine  and  feces  together  contained  21.16  grams 
of  phosphoric  acid  with  a  daily  average  of 
2.12  grams.  During  this  same  time  the  food 
contained  20.29  grams  of  phosphoric  acid  with 
a  daily  average  of  2.03  grams.  These  results 
thus  indicate  a  slight  loss  of  phosphoric  acid 
during  the  ten-day  period  in  question,  but  the 
loss  is  so  small  as  to  fall  nearly  within  the 
limits  of  experimental  error,  and  hence  is  to 
be  disregarded. 

The  Fat  Loss  by  the  Feces,  In  all  of  the 
cases  of  infantilism  it  has  been  noteworthy 
that    the    stools    have    been    excessively    fatty, 


INFANTILISM]  49 

even  where  only  moderate  quantities  of  fat 
have  been  taken  with  the  food.  The  presence 
of  large  amounts  of  fatty  acids  has  already 
been  referred  to  in  speaking  of  the  appear- 
ances of  the  feces  in  these  cases.  Another 
characteristic  is  the  presence  of  soaps,  the 
white  masses  of  which,  looking  like  small 
granular  coagula  of  casein,  sometimes  give  a 
very  noteworthy  appearance  to  the  stools. 
These  masses  of  white  soaps  (probably  calcium 
soaps)   have  often  been  mistaken  for  casein. 

In  Case  I  the  fats  of  the  feces  were  sub- 
jected to  careful  study.  It  was  found  that  the 
total  percentage  of  fats  in  the  solids  was 
uniformly  high  even  on  a  diet  containing  only 
moderate  amounts  of  fat.  Thus  at  different 
periods,  lasting  from  two  to  ten  days,  the  per- 
centages of  fats  of  the  solids  of  the  feces 
amounted  to  29.80,  31.93,  32.78,  44.60,  39.21, 
41.96,  47.26,  40.90,  25.01,  39.66,  36.16.  These 
figures  include  not  merely  the  ethereal  ex- 
tracts, but  also  the  fatty  acids  in  the  form  of 
soaps.  They  therefore  represent  the  total  fats 
lost.  It  will  be  seen  that  these  figures  repre- 
sent a  large  loss  of  fat  of  the  food.  The 
actual  loss  of  fat  for  various  periods  is  shown 
by  the  following  table,  which  shows  also  the 
losses  of  soaps  and  the  losses  of  calcium  com- 
bined as  soaps  (assuming  the  soaps  to  con- 
sist wholly   of   soaps   of   calcium) : 


50 


INFANTILISM 


Table  I 
Showing  actual  loss  of  fat  with  feces  during  various  periods: 
Case  I 


Total  fats  Soaps  Calcium  Oxide 

per                           per  from  soaps 

period  period  per  period 

Date  of  Period                Grams  Grams  Grams 

Dec.  2,  6,  8,   '07 21.6                      1.46  0.145 

Dec.  13,  14,  19,  20,   '07..   23.8                     0.93  0.092 

Dec.  20,  21,   '07 22.2                     3.16  0.313 

Dec.  25,  29,  31,    '07 20.9                      2.69  0.266 

Jan.  19,  20,    '08 13.0                      2.61  0.258 

Jan.  26,  27,    '08 17.0                     4.20  0.416 

Feb.  8,  9,  10,    '08 29.2                     4.67  0.463 

Feb.  14,  15,  16,  17,  '08..   32.1                     4.74  0.469 

March  10  to  20,    '08 55.6  10.80  1.070 

Comparing  these  figures,  representing  tlie  loss 
of  fat,  with  the  figures  representing  the  intake 
of  fat  during  one  of  the  periods  studied 
(March  10-20,  1908)  it  was  found  that  the  per- 
centage of  fat  absorbed  was  85.5,  while  the 
percentage  of  fat  lost  was  14.5.  These  figures 
indicate  the  considerable  extent  to  which  the 
fat  is  lost  in  these  cases  on  a  diet  containing 
only  a  moderate  amount  of  fat,  since  in  a 
normal  individual  one  would  look  for  a  fat 
absorption  of  from  92  to  98  per  cent.  But 
these  figures  relate  to  a  period  of  improve- 
ment and  by  no  means  show  the  worst  fat 
absorption  noted  in  Case  I.  At  an  earlier 
period,  with  the  same  daily  intake  of  fat 
(38.28  grams),  the  losses  were  frequently  from 
20  to  25  per  cent.,  and  once  reached  40  per 
cent,    of   the   ingested   fat. 


INFANTILISM  51 

Observations  have  been  made  in  Case  I  rela- 
tive to  the  proportions  existing  between  the 
neutral  fats,  the  fatty  acids  and  the  soaps. 
They  show  that  fat  splitting  and  saponifica- 
tion have  occurred  in  high  degree  in  the  intes- 
tinal tract,  since  the  fatty  acids  range  from 
40.75  per  cent,  to  80.25  per  cent.,  while  the 
soaps  vary  from  3.89  per  cent,  to  20.08  per 
cent.  The  neutral  fats,  on  the  other  hand, 
range  from  6.88  to  39.85  per  cent.  It  is 
thus  evident  that  the  greater  part  of  the  fats 
lost  are  in  the  form  of  fatty  acids  and  that 
the  sum  of  the  fatty  acids  and  the  soaps  make 
up  on  the  average  about  three  quarters  of  the 
total  fat  lost.  These  losses  cannot,  of  course, 
be  attributed  to  any  failure  of  fat  splitting 
in  the  intestine,  but  are  clearly  referable  to  a 
diminished  power  of  absorption.  It  is  note- 
worthy that  so  considerable  a  percentage  of 
the  total  fats  lost  is  in  the  form  of  soaps  of 
the  fatty  acids.  The  importance  of  this  fact 
lies  in  the  consideration  that  these  soaps  are 
for  the  most  part  calcium  and  magnesium 
soaps  (chiefly  the  former),  and  that  they 
represent  a  loss  of  calcium  and  magnesium 
to  the  organism  dependent  on  non-absorption 
of  the  soaps  of  these  alkaline  earths.  It  is 
true  that  only  a  relatively  small  percentage 
(say  10  per  cent.)  of  the  calcium  lost  in  the 
feces  is  present  in  the  form  of   soaps,  but  it 


52  INFANTILISM 

is  obvious  that  the  non-absorption  of  the  quan- 
tity of  calcium  represented  by  this  proportion 
is  enough  to  determine  whether  the  organism 
shall  or  shall  not  gain  calcium  for  the  pur- 
pose of  building  up  the  skeleton.  The  same 
considerations   hold  true   also  of  magnesium. 

Let  us  take  a  specific  example  relating  to 
calcium.  Between  March  10  and  20  there 
was  a  loss  of  10.8  grams  of  soaps.  These 
soaps  consist  almost  entirely  of  soaps  of  cal- 
cium and  have  been  calculated  as  such  in  the 
foregoing  table.  On  this  assumption  the  cal- 
cium oxide  representing  these  soaps  would 
amount  to  1.07  grams.  For  a  period  of  one 
year  the  calcium  oxide  thus  lost  as  soaps 
would  amount  to  more  than  36  grams.  The 
gain  of  so  much  calcium  by  the  skeleton,  or 
its  loss  through  the  feces,  is  clearly  an  im- 
portant   element   in   the    skeletal    growth.^ 

*  I  have  calculated  that  the  average  yearly  accretion  of  calcium 
oxide  by  the  skeleton  between  the  third  and  sixteenth  year  is  51.6 
grams.  If  we  deduct  36  grams  of  calcium  oxide  as  representing 
the  loss  through  soaps,  we  see  that  there  will  be  left  but  little 
calcium  for  the  purpose  of  skeleton  building. 

The  above  result  was  reached  by  the  following  data: 
Estimate  of  the  average  yearly  addition  of  calcium  (as  calcium 
oxide)    to   the   human  skeleton   between   the   third   and   sixteenth 
year. 

Weight  of  body  at  3  years 16  kilos 

Weight  of  body  at  16  years 50  kilos 

Estimated  weight  of  skeleton  in  %  of  total  at  3  years. . .   15% 
Estimated  weight  of  skeleton  in  %  of  total  at  16  years.  .   17% 

Weight  of  skeleton  at  3  years 2.4  kilos 

Weight  of  skeleton  at  16  years 8.5  kilos 


INFANTILISM  53 

PATHOIiOGY 

It  is  desirable  to  consider  the  data  that 
have  been  presented  in  the  foregoing  pages 
with  a  view  to  their  bearing  on  the  pathology 
of  intestinal  infantilism.  It  is  believed  that 
the  data  now  available  suffice  to  form  a  con- 
ception of  the  nature  of  the  processes  that 
underlie  this  serious  disorder  of  nutrition,  even 
if  they  do  not  serve  to  satisfactorily  clear  up 
all  questions  relating  to  the  etiology  of  the 
affection.  There  are  two  large  and  distinct 
but  related  features  of  intestinal  infantilism 
which  must  be  taken  into  account  in  any 
endeavor  to  understand  the  morbid  processes 
on  which  the  clinical  manifestations  depend. 
These  are,  first,  the  extreme  retardation  in 
general  bodily  development,  secondly,  the  state 

Undried  bone  contains  22%  of  bone  earth 

Skeleton  of  2.4  kilos  contains  0.53  kilo  bone  earth 

Skeleton  of  8.5  kilos  contains  1.87  kilos  bone  earth 

Accretion  of  bone  earth  by  skeleton  between  the  age  of  3  and 

16  years  equals  1.34  kilos 
Bone  earth  contains  approximately  84%  calcium  phosphate 
Bone  earth  contains  approximately  13%  calcium  carbonate 
1.34  kilos  bone  earth  contain  1.125  kilos  calcium  phosphate 
1.34  kilos  bone  earth  contain  0.175  kilos  calcium  carbonate 
1.125  kilos  calcium  phosphate  contain  0.60  kilos  calcium  oxide 
0.175  kilo  calcium  carbonate  contains  0.07  kilos  calcium  oxide 
Total  calcium  oxide  in  1.34  kilos  

of  bone  earth  =  0.67  kilos  calcium  oxide 

This  represents  the  accretion  of  calcium  oxide  during  thirteen 
jears  of  skeletal  growth.  The  yearly  average  accretion  of  calcium 
oxide  in  skeletal  growth  between  these  years  therefore  equals 
0.0516  kilos  or  51.6  grams. 


54  INFANTILISM 

of  intoxication  which  manifests  itself  in  promi- 
nent derangements  of  the  neuromuscular  system. 

The  Retardation  in  Development,  The  re- 
tardation in  the  development  of  the  body 
implicates,  as  already  stated,  the  skeleton, 
muscles,  fat  and  viscera  generally,  while 
slowing  the  growth  of  the  brain  in  relatively 
slight  degree.  Where  are  we  to  seek  for  an 
explanation  of  the  actual  check  to  the  general 
growth  and  the  disparity  in  state  of  bodily 
nutrition  as  compared  with  that  of  the  brain? 

The  retardation  in  growth  undoubtedly  de- 
pends in  the  main  on  a  simple  cause — insuffi- 
ciency of  the  foodstuffs  absorbed  from  the 
digestive  tract.  Such  insufficiency  of  absorp- 
tion may  be  referable  to  an  inadequate  food 
supply  or  to  imperfect  absorption  of  food- 
stuffs from  the  tract.  The  dietetic  conditions 
in  our  cases  were  of  such  a  nature  as  not  to 
exclude  the  former  factor,  although  making 
impaired  absorption  largely  responsible  for  the 
diminished  supply  of  food  materials  available 
for  the  growth  of  the  body.  In  thus  stating 
the  case  no  allowance  is  made  for  the  pos- 
sibility that  there  may  be  disturbances  of 
metabolism  wliich  make  for  the  impaired  util- 
ization of  foodstuffs  after  their  absorption. 
It  will  be  pointed  out  in  the  course  of  this 
discussion  that  metabolic  derangements  do  to 
some  extent  exist,  but  that  they  are  to  be  con- 


INFANTILISM  55 

sidered  as  secondary  to  the  absorption  of 
mildly  toxic  but  continually  formed  products. 
The  following  considerations  will,  I  believe, 
serve  to  show  that  the  leading  cause  of  the 
arrest  of  growth  is  neither  deficient  food^  nor 
specific  disorders  of  metabolism,  but  serious 
defects  in  digestion  and  absorption  which  find 
expression  in  a  failure  of  the  organism  to  get 
its  proper  share  of  nutritious  materials  from 
the  digestive  tube.  These  defects  may  be  con- 
sidered from  the  standpoint  of  the  carbo- 
hydrates, the  fats,  the  proteins  and  the  salts 
respectively. 

It  has  been  pointed  out  that  a  prominent 
feature  in  the  nutritional  history  of  intestinal 
infantilism  is  the  intolerance  for  carbohydrates, 
which  even  in  moderate  amounts  lead  quickly 
to  soft  or  diarrhoeal  movements,  often  with 
an  increase  in  mucus  and  sometimes  with  a 
markedly  excessive  formation  of  intestinal  gases. 
Even  if  the  disturbances  incidental  to  the 
moderate  use  of  carbohydrates  are  for  a  time 
at  least  less  obtrusive  than  those  just  men- 
tioned, the  physician  is  ultimately  convinced 
that  his  patient  is  freest  from  intestinal  symp- 
toms   when    this    class    of    foodstuffs    is    much 

^  It  is  true  that  in  each  of  the  five  cases  there  were  times  when 
the  food  was  deficient  in  amount,  but  in  all  instances  repeated 
efforts  were  made  (sometimes  unsuccessfully)  to  increase  the  food 
supply  sufficiently  to  make  it  enough  for  the  needs  of  normal  chil- 
dren of  corresponding  weight,  or  even  in  excess  of  their  needs. 


56  INFANTILISM 

restricted.  This  conviction  lias  the  practical 
result  that  the  child  is  in  considerable  degree 
deprived  of  that  class  of  foodstuffs  on  which 
the  organism  mainly  depends  for  its  caloric 
needs.  The  formation  of  adipose  deposits  de- 
pends in  childhood,  in  at  least  a  measure,  on 
the  ability  of  the  organism  to  appropriate 
carbohydrates  in  greater  quantity  than  is 
necessary  to  maintain  the  body  weight,  this 
surplus  being  clearly  convertible  into  fat  by 
obscure  synthetic  processes.  Under  normal 
conditions  it  is  further  probable  that  the  sugars 
and  starches  furnish  a  portion  of  the  material 
used  in  the  upbuild  of  the  living  protoplasm 
generally,  especially  that  of  the  muscles  and 
parenchymatous  organs.  But  from  experience 
with  diabetic  persons  and  from  various  physio- 
logical facts  we  know  that  these  functions  of 
the  carbohydrates  may  be  in  large  degree  sub- 
stituted by  the  fats  and  proteins  of  the  food. 
The  development  of  a  diabetic  child  is  possible 
if  the  carbohydrates  are  replaceable  by  these 
other  foodstuffs,  but  only  in  this  case.  The 
same  statement  probably  holds  equally  true 
of  many  children  suffering  from  digestive 
derangements.  It  being  necessary  to  deprive 
our  patients  with  infantilism  to  a  considerable 
extent  of  their  carbohydrates,  we  turn  with 
especial  interest  to  learn  how  these  children 
dispose   of  their  fats  and  proteins. 


INFANTILISM  57 

The   fats    are   on   the   whole   better   tolerated 
than   the    carbohydrates    by    our    patients    with 
intestinal    infantilism.     That    is    to    say,    if   we 
give   to   a   child   whose   caloric  needs   are   1000 
calories  per  diem,  100  grams  of  carbohydrates 
or   its    approximate    caloric    equivalent   in   fats 
(say  50   grams   of  fat),    the   latter   may   cause 
less  obvious  disturbances  of  function  than  the 
former.    But    from   this    we    are    not    justified 
in  concluding  that  the  fats  are  in  reality  well 
utilized.     They  may   be  tolerated  in   the   sense 
that  they  do  not  promptly  bring  on  obtrusive 
symptoms,   but   examination   of   the   movements 
shows  that  the  absorption  of  fats  is  far  below 
the    standard    for    health,    as    regards    neutral 
fats,   fatty   acids   and   soaps.     Thus   in   Case   I 
there  was  during  a  period  of  two  days  of  fat 
diarrhoea  a  loss  of  22.2  grams  of  fat   (neutral 
fat,    fatty    acids    and    soaps)     or    11.1    grams 
daily.     This  large  loss  in  fat  represents  nearly 
40  per  cent,  of  the  fat  intake  at  the  time  and 
is  equivalent  to  a  waste  of  about  100  calories 
daily.     Losses   of   from   seven    to    eight    grams 
of  fat  daily  were  common,  representing  25  per 
cent,   of   the   fat   ingested.    In   this    great   loss 
of  fat  we  have   the   key  to   the   understanding 
of    the    failure    in    nutrition    which    constitutes 
the    most   prominent    feature    of   intestinal    in- 
fantilism. 


58  INFANTILISM 

It  is  obvious  that  such  a  fat  loss  (and  the 
exam]Dle  is  representative  of  the  cases  which 
have  up  to  the  present  come  to  my  notice, 
having  been  also  marked  in  Cases  II,  III  and 
IV),  when  added  to  an  intolerance  for  carbo- 
hydrates, can  lead  to  nothing  less  than  a  state 
of  well-defined  under-nutrition.  We  can  imitate 
this  condition  by  withholding  fats  in  large 
degree  from  young  animals.  In  making  this 
experiment  with  young  puppies  and  with  young 
pigs  I  found  it  easy  to  prevent  any  increase 
in  weight  notwithstanding  milk  proteins  were 
given  much  in  excess  of  ordinary  requirements, 
together  with  the  milk  sugar  naturally  present 
in  milk.  I  therefore  believe  that  the  incapacity 
to  absorb  fats  and  carbohydrates  is  in  itself 
sufficient  to  explain  a  state  of  infantilism  in 
the  human  subject  despite  the  free  use  of 
proteins.  It  will  be  seen,  however,  that  the 
failure  to  absorb  fats  entails  two  other  con- 
sequences which  lend  their  influence  to  hinder 
development — a  loss  in  calcium  and  magnesium 
salts  and  an  increase  in  intestinal  jDutrefac- 
tion.  Before  discussing  these  factors  in  the 
pathology  of  infantilism,  it  is  desirable  to  con- 
sider the  fate  of  the  ingested  proteins. 

A  study  of  the  nitrogen  balances  (for  three 
separate  periods)  derived  from  a  comparison 
of  the  nitrogen  ingested  with  the  nitrogen  lost 
with   the   urine   and   feces    (in   Case    I)    shows 


INFANTILISM  59 

that  only  an  insignificant  amount  of  nitrogen 
(0.65  gm.  in  10  days)  was  retained.  This  is,  of 
course,  a  not  surprising  result  if  we  consider 
the  very  small  gain  of  the  patient  in  weight; 
and  there  is  no  reason  to  doubt  that  this 
result,  derived  from  a  study  of  Case  I,  could 
have  been  paralleled  by  studies  of  the  nitrogen 
balances  in  any  of  the  other  cases  of  infan- 
tilism during  the  period  of  almost  total  arrest 
in  growth. 

Table  II 
Showing  the  intake  of  nitrogen  with  the  food  and  loss  of  nitro- 
gen with  the  feces,  according  to  periods. 
Case  I 

N  of  Food  N  of  Feces  Loss  of  N 

Grams  Grams  Per  cent. 

Period  I   (3  days) 22.89  2.34  10.2 

Period  II   (4  days) 29.03  4.39  14.7 

Period  III   (10  days) 66.46  8.44  12.5 

Total  N  in  Total  N  in  Gain  or  loss  Average  daily 

Urine           Urine  +  in  N  per  gain  or  loss 

Grams             Feces            period  in  N 

Grams  Grams  Grams 

Period  I   (3   days)  .  .  .    19.07           21.41  -|-1.48  -f  0.49 

Period  II   (4  days)  .  .   24.66           29.05  —0.02  —0.005 

Period  III   (10  days)   56.36           64.80  +1.66  -[-0.166 

If  we  look  at  the  figures  in  Table  II  which 
relate  to  the  absorption  of  nitrogen  from  the 
digestive  tract,  for  the  periods  in  question  in 
Case  I,  we  note  that  the  absorption  of  protein 
(as  measured  by  its  nitrogen  content)  is  not 
so  complete  as  it  should  be.  In  period  I,  cov- 
ering three  days,  the  nitrogen  of  the  food  was 
22.89  grams  and  that  of  the  feces  2.34  grams. 
The  loss  of  nitrogen  by  the  feces  in  this  period 


60  INFANTILISM 

was  10.2  per  cent.  In  period  II,  covering  four 
days,  the  nitrogen  of  the  food  was  29.03  grams, 
the  nitrogen  of  the  feces,  4.39  grams.  The 
nitrogen  lost  by  the  feces  in  this  period  was 
14.7  per  cent.  In  period  III  the  food  con- 
tained 66.46  grams  of  nitrogen  and  the  feces 
8.44  grams.  Here  the  loss  in  nitrogen  equaled 
12.5  per  cent.^  In  health  the  loss  of  nitrogen 
by  the  feces  under  comparable  conditions  of 
protein  feeding  is  not  greater  than  7  or  8  per 
cent,  of  the  nitrogen  ingested.  So  we  may 
say  that  the  protein  absorption  in  Case  I  was 
somewhat  under  90  per  cent,  instead  of  92  per 
cent,  or  over.  Protein  absorption  is  therefore 
relatively  much  better  than  the  absorption  of 
fat,  despite  the  fact  that  it  is  somewhat 
impaired. 

Our  interest  in  the  fate  of  the  inorganic 
salts  centers  about  the  alkali  earths.  It  has 
been  made  out  that  in  Case  I,  where  a  careful 
balance  was  made  of  the  calcium  and  mag- 
nesium, the  organism  failed  to  gain  either  of 
these  elements.  Under  these  conditions  it  is 
not  surprising  that  the  skeleton  should  remain 
stationary  in  weight.  In  a  healthy,  growing 
child,  weighing  25  pounds,  there  should  be 
definite   evidence  of   the   absorption   of  calcium 

*  Some  portion  of  the  nitrogen  of  the  feces  is  attributable  to 
the  epithelial  detritus  present  here  in  excess,  but  it  is  difficult  to 
make  a  fair  allowance  for  this. 


INFANTILISM  61 

and  magnesium  in  quantitievS  sufficient  to  account 
for  the  uninterrupted  and  rapid  growth  of  the 
skeleton  during  infancy   and   childhood. 

Even  under  wholly  normal  conditions  the 
quantity  of  calcium  daily  absorbed  from  the  in- 
testine of  a  young  child  is  small,  while  the 
loss  of  calcium  by  the  feces  is  large.  Thus  in 
a  normal  child  of  nine  months  the  feces  con- 
tained 2.122  grams  of  calcium  (estimated  as 
oxide),  while  the  food  contained  only  a  little 
more  than  this — 2.194  grams.^  It  is  perfectly 
obvious  that  any  influence  which  tends  to 
diminish  the  absorption  of  this  small  propor- 
tion of  the  ingested  calcium  must  jeopardize 
the  small  daily  supply  of  this  element  which 
is  required  for  the  growth  of  the  skeleton. 
And  it  is  important  to  note  that  in  some 
apparently  healthy  children  the  maintenance  of 
a  positive  or  negative  calcium  balance  is 
determined  by  apparently  so  slight  a  factor 
as  the  variation  in  the  percentage  of  fat  in 
the  milk.  Thus  Eothberg^  found  that  the  use 
of  skimmed  milk  insured  a  positive  calcium 
balance  (even  in  some  children  with  definite 
signs  of  rickets),  whereas  in  a  certain  number 
of  children  the  use  of   full-fat  milk   caused  a 

*  See  O.  Eothberg.  ' '  TJeber  den  Einfluss  der  organischen 
Nahrungskomponenten  auf  den  Kalkumsaltz  kunstlich  genahrten 
Saulinge. "  Jahri.  f.  Einderheillc.j  66,  der  dritten  Folge, 
16  Band,  Heft  1,  1907. 

'Log.  cit. 


62  INFANTILISM 

marked  negative  balance.  Quite  similar  results 
were  obtained  by  Birk^  in  his  study  of  tbe 
magnesium  metabolism  in  nurslings.  And  it 
may  be  further  noted  that  both  in  the  case  of 
calcium  and  magnesium  a  negative  balance 
may  be  induced  in  some  children  by  the  free 
use  of  carbohydrates,  for  reasons  at  present 
not  clear. 

It  has  been  several  times  mentioned  that  a 
leading  feature  in  the  pathology  of  infantilism 
is  the  large  loss  in  fat  by  the  feces.  A  portion  of 
this  fat  (varying  in  Case  I  from  14  to  20  per 
cent,  of  the  total  fat  lost)  is  present  as  soaps 
and  especially  as  soaps  of  calcium.  If  we  as- 
sume that  the  soaps  of  the  feces  exist  as  soaps 
of  calcium  (an  assumption  not  far  from  the 
truth,  since  magnesium  soaps  are  present  in 
only  small  proportion)  it  is  clear  that  the  loss 
of  saponified  fat  entails  a  significant  loss  of 
calcium.  Thus  in  Case  I  the  loss  in  soaps  during 
a  ten-day  period  amounted  to  19.8  grams,  cor- 
responding to  a  withdrawal  of  1.07  grams  of  cal- 
cium oxide  during  the  same  time.  This  is  a 
quantity  of  calcium  sufficiently  large  to  be  of 
the  first  importance  to  the  skeleton,  for  in  a 
case  where  there  is  practically  no  gain  and  no 
loss  in  skeletal  calcium,  a  positive  balance  would 
be  established  by  the  absorption  and  appropriation 

"^TJeber  den  Magnesimnsaltz  des  Saulings."    Jahrh.  f.  Kin- 
derheiXk.,  66  der  dritten  Folge,  16  Band,  Heft  3,  1907. 


INFANTILISM  63 

of  any  portion  of  the  calcium  habitually  lost 
as  soap.  The  utilization  of  the  entire  amount 
of  calcium  present  as  soap  would  make  possible 
a  fair  skeletal  growth;  and  I  have  calculated 
that  the  full  absorption  of  this  calcium  (through 
improved  soap  absorption)  would  in  itself  be 
almost  enough  to  account  for  a  wholly  normal 
skeletal  development.  It  is  possible,  however, 
that  in  order  to  secure  normal  skeletal  growth 
we  should  have  to  obtain  a  somewhat  improved 
absorption  of  calcium  not  present  as  soap.  I 
cannot  further  discuss  this  point  for  I  do  not 
know  enough  of  the  conditions  attending  physio- 
logical fat  absorption. 

Sufficient  evidence  has  now  been  brought  for- 
ward to  support  the  contention  that  the  arrested 
growth  of  infantilism  can  be  explained  by  the 
inability  of  the  organism  to  secure  an  adequate 
supply  of  nutrient  materials  from  the  lumen  of 
the  digestive  tract.  The  failure  to  absorb  suf- 
ficient calcium  and  magnesium  accounts  for  the 
arrest  of  skeletal  growth ;  the  restricted  absorp- 
tion of  carbohydrates  and  fats  explains  the 
failure  to  lay  up  fat,  and  at  least  partially  ac- 
counts for  the  cessation  in  the  growth  of  muscle. 
The  proportionate  retardation  in  the  growth  of 
the  viscera  doubtless  has  a  similar  origin  although 
possibly  here  the  physiological  adaptation  of  vis- 
ceral structures  to  the  needs  of  the  rest  of  the 
body  may  have  an  influence.    The  relatively  large 


64  INFANTILISM 

size  of  the  head  and  brain  may  be  in  part  due 
to  the  large  size  of  the  brain  at  birth,  but  it 
appears  that  the  growth  of  the  brain  in  infan- 
tilism is  somewhat  out  of  proportion  to  the  very 
slow  development  or  entire  arrest  of  the  body 
in  general.  This  is  perhaps  attributable  to  the 
protected  position  of  the  central  nervous  sys- 
tem, in  the  sense  that  it  not  merely  exercises 
a  kind  of  first  call  on  the  nutritive  materials 
which  it  requires  but  is  also  in  large  measure 
screened  from  the  action  of  certain  poisonous 
substances  by  the  action  of  the  liver,  muscles, 
etc. 

The  leading  feature  of  infantilism — the  pro- 
longed arrest  of  development  in  early  childhood — 
is  thus  seen  to  be  due  to  an  impaired  power 
of  absorption  of  nutrient  materials  in  so  far  as  it 
depends  on  a  lack  of  available  fats,  salts  and 
proteins.  The  relation  between  insufficient  car- 
bohydrates and  defective  absorption  is  less  simple, 
for  the  restriction  in  this  class  of  foodstuffs  is 
often  one  encouraged  by  the  physician  on  ac- 
count of  the  evil  consequences  following  even 
the  moderate  use  of  sugars  and  starches.  Prob- 
ably a  failure  on  the  part  of  the  intestine  to 
promptly  absorb  the  dextrose  formed  during 
the  digestion  of  starches  is  a  factor  in  depriv- 
ing the  organism  of  its  proper  share  of  car- 
bohydrates, but  this  would  perhaps  not  suffice 
to  make  this  deprivation  significant  but  for  the 


INFANTILISM  65 

intervention  of  a  second  factor,  namely  the 
excessively  rapid  decomposition  of  dextrose  by 
bacteria. 

The  impaired  power  of  absorbing  foodstuffs 
from  the  intestinal  tract  I  believe  to  be  refer- 
able to  a  chronic  inflammatory  process  impli- 
cating especially  the  lower  lengths  of  the  small 
intestine  and  perhaps  the  contiguous  portion  of 
the  colon.  This  inference  is  based  in  part  on 
the  occurrence  of  mucus  and  epithelial  cells 
intimately  mingled  with  the  intestinal  contents 
and  partly  on  certain  resemblances  between  the 
signs  of  chronic  saccharo-butyric  putrefaction 
in  adults,  a  condition  in  which  there  is  direct 
evidence  of  congestion  and  inflammation  of  the 
mucous  membrane  of  the  ileum  and  colon.  The 
inflammation  of  the  digestive  tract  in  infantil- 
ism can  be  confidently  attributed  to  the  pres- 
ence and  dominance  of  an  unsuitable  bacterial 
flora. 

It  is  likewise  to  this  unsuitable  bacterial  flora 
that  we  have  to  attribute  the  excessive  putre- 
factive decompositions  in  the  intestinal  tract  on 
which  depends  the  second  leading  group  of 
symptoms  of  intestinal  infantilism — namely  the 
chronic  intoxication  of  the  neuromuscular  sys- 
tem which  is  in  every  case  discernible.  Among 
the  products  of  putrefaction  in  the  intestine 
are  indol,  indolacetic  acid,  phenol  and  the  aro- 
matic   oxyacids.    We    know    that    indol    exerts 


66  INFANTILISM 

an  irritant  action  on  the  central  nervous  sys- 
tem, an  action  which  if  long  continued  leads 
to  depression  of  function.  Likewise  the  de- 
pressant action  of  indol  on  the  muscles  is  well 
marked.^  Of  the  action  of  the  other  aromatic 
putrefactive  substances  on  the  neuromuscular 
system  little  is  positively  known.  Clinical  ob- 
servation makes  me  think  that  indolacetic  acid 
may  exert  an  action  similar  to  that  of  indol, 
but  milder  in  intensity.  The  fact  that  the 
signs  of  intoxication  (emotional  irritability  and 
depression,  rapid  muscle  fatigue)  undergo  strik- 
ing amelioration  coincidentally  with  a  marked 
fall  in  the  quantity  of  the  aromatic  putre- 
factive substances  in  the  urine  seems  a  reliable 
indication  that  the  neuromuscular  intoxication 
is  related  to  the  excessive  absorption  of  such 
putrefactive  substances  from  the  digestive  tract. 
There  is  another  aspect  of  this  excessive  putre- 
faction which  must  not  be  overlooked  in  any 
discussion  of  the  pathology  of  infantilism, 
namely  the  loss  of  food  material  which  it 
entails.  As  an  instance  we  may  take  the  case 
of  tryptophan  and  indolacetic  acid.  The  latter 
is  sometimes  formed  in  such  large  quantities 
from  the  former,  in  the  course  of  putrefaction, 
as  to  rob  the  organism  of  a  not  insignificant 
quantity    of    tryptophan — an    amino-acid    which 

^  See  experiments  cf  F.  S.  Lee,  mentioned  in  my  volxmie,  Com- 
mon Bacterial  Infections  of  the  Digestive  Tract,  p.  255. 


INFANTILISM  67 

there  is  every  reason  to  regard  as  essential  to 
nutrition.  There  may  be  a  similar  loss  of 
tyrosin  owing  to  the  putrefactive  conversion  of 
this  amino-acid  into  aromatic  oxyacids  in  the 
intestinal  tract.  Finally  it  must  be  regarded 
as  an  open  question  whether  the  products  of 
putrefaction,  after  absorption,  may  not  have 
some  damaging  influence  on  the  processes  of 
metabolism  themselves  through  their  action  on 
cells  entrusted  with  important  assimilative 
powers. 

The  two  cardinal  features  of  infantilism, 
arrest  of  bodily  growth  and  the  group  of 
symptoms  based  on  chronic  intoxication,  thus 
have  their  origin  in  an  abnormal  intestinal 
flora  possessed  of  a  high  degree  of  parasitism 
owing  to  a  long  period  of  adaptation.  The 
nature  of  the  pathological  flora  has  been  already 
described  in  so  far  as  it  has  been  studied  in 
a  small  number  of  typical  examples  of  intes- 
tinal infantilism.  The  interpretation  of  these 
findings  can,  however,  be  undertaken  only  with 
much  caution,  owing  to  the  scantiness  of  our 
real  knowledge  of  the  biological  characters  of 
the  microorganisms  which  we  have  found  to 
be  so  regularly  and  persistently  associated  with 
intestinal  infantilism.  The  evidence  on  which 
we  must  base  a  judgment  is  circumstantial 
rather  than  direct.  It  is  unlikely  that  the 
pathological  state  can  be  experimentally  repro- 


68  INFANTILISM 

duced  in  animals  by  means  of  the  organisms 
which  we  have  fonnd  to  be  characteristic  of 
the  chronic  human  infection.  The  ordinary 
tests  of  pathogenicity  have  given  negative 
results  with  the  three  types  of  organisms 
which  appear  most  intimately  related  to  the 
infection,  namely  B,  hifidus,  B.  infantilis  and 
the  cocco-bacillary  forms.^  In  other  words,  we 
cannot  here  apply  the  criteria  that  have  served 
so  well  in  studying  acute  infectious  diseases. 
There  are,  nevertheless,  certain  obtrusive  phe- 
nomena which  cannot  be  overlooked  and  which 
call  for  some  comment.  The  great  abundance 
of  B,  hifidus  in  the  formed  and  diarrhoeal 
stools  of  infantilism,  and  in  the  mucus  con- 
tiguous to  the  mucosa,  suggests  a  relationship 
of  a  causative  nature  to  the  inflammatory 
process  within  the  gut.  This  suggestion  is 
made  the  more  reasonable  by  the  fact  that 
periods  of  improvement  in  absorption  (due 
presumably  to  amelioration  in  the  intensity  of 
the  inflammation)  have  been  associated  in 
numerous  instances  with  a  partial  disappear- 
ance of  B.  hifidus  from  the  stools  or  through 
a  modification  in  the  morphology  of  the  organ- 
ism pointing  plainly  to  a  decline  in  vigor.  It 
is  perhaps  true  that  the  same  argument  might 

*It  should  be  stated  that  a  dog  was  fed  on  milk  inoceulated 
with  B.  infantilis  after  sterilization.  The  animal  developed  a 
persistent  diarrhoea  which  ceased  only  with  the  discontinuation  of 
the  infantilis  milk.    A  second  trial  gave  a  similar  result. 


INFANTILISM  69 

be  applied  with  equally  good  reason  to  the 
relation  of  B,  infantilis  to  infantilism,  except 
that  we  have  not  found  this  organism  in  the 
mucus.  Finally  the  fact  must  be  mentioned 
that  the  disappearance  of  B.  hifidus  and  B, 
infantilis  has  been  noticed  to  be  concomitant, 
not  only  with  clinical  improvement,  but  with 
an  increase  in  the  numbers  of  the  cocco-bacillary 
forms  which  are  apparently  always  present. 
This  fact  seems  to  indicate  that  this  group  of 
organisms  is  less  objectionable  than  the  micro- 
organisms which  it  replaces.  A  fact  which 
calls  for  especial  comment  is  the  occurrence 
of  B.  hifidus  and  B.  infantilis  in  the  stools  of 
normal  infants  and  in  small  numbers  in  some 
healthy  adults.  Tissier  and  other  French  ob- 
servers have  insisted  on  the  presence  of  B. 
hifidus  in  the  stools  of  nurslings,  even  main- 
taining that  this  microorganism  is  the  charac- 
teristic and  dominant  one.  It  is  necessary  to 
reconcile  this  contention  with  the  suspicion  just 
expressed  that  B,  hifidus  is  actually  an  inju- 
rious agent  in  our  cases  of  infantilism.  In 
this  connection  it  is  important  to  state  at  the 
outset  that  the  study  of  many  Gram- stained 
smears  from  normal  nurslings  indicates  that 
in  the  United  States  there  are  numerous 
normal  nurslings  from  whom  one  can  obtain 
no  evidence  of  the  presence  of  B.  hifidus  in 
the  stools;  and  this  assertion  is   supported  by 


70  INFANTILISM 

the  results  of  careful  cultural  procedures  car- 
ried on  by  experienced  persons.  On  the  other 
hand,  B,  hifidus  did  appear  in  the  cultures 
from  some  of  the  normal  nurslings'  stools 
examined  by  us;  and  in  some  instances  the 
Gram-stained  fecal  fields  showed  a  great  abun- 
dance of  positive  forms  possessing  a  mor- 
phology indistinguishable  from  the  plain  form 
of  B,  hifidus.  But  there  are  two  comments  to 
be  made  on  these  findings.  First,  we  have 
never  been  able  to  obtain  in  plate  cultures  so 
many  bifidus  organisms  from  normal  nurslings 
as  from  cases  of  infantilism,  and  it  seems  a 
safe  inference  that  these  bacteria  are  in  reality 
more  abundantly  present  (in  at  least  some 
cases  of  infantilism)  than  in  healthy  nurslings. 
Secondly,  it  must  be  plainly  stated  that  there 
is  no  sound  evidence  that  the  greater  number 
of  the  Gram- stained  positive  bifidus-like  bac- 
teria in  the  nurslings'  stools  are  in  reality 
examples  of  B.  hifidus.  The  French  writers 
have  assumed  that  the  organisms  seen  in  the 
fecal  fields  are  bifidus,  but  the  contention  has 
never,  I  believe,  been  successfully  sustained  by 
adequate  cultural  methods.  We  know  that  B. 
infantilis  and  some  acidophile  bacteria  (other 
than  B,  hifidus,  which  is  to  be  ranked  as  an 
acidophile  microorganism  in  the  sense  of 
being  able  to  grow  in  a  strongly  acid  medium, 
though  not  in  the  sense   of  being  restricted  in 


INFANTILISM  71 

growth  in  a  neutral  medium)  may  exist  in 
fecal  fields  side  by  side  with  the  plain  form 
of  B,  hifidiis  and  indistinguishable  from  it. 

Thus  such  evidence  as  is  now  available  indi- 
cates that  B.  hifidus  is  considerably  more  abun- 
dant in  the  stools  of  infantilism  than  in  the 
stools  of  normal  nurslings.  It  may  be  that 
any  detrimental  action  exerted  by  these  bac- 
teria is  due  to  their  relative  predominance  in 
the  intestinal  tract  of  infantilism,  perhaps  also 
to  a  failure  in  a  normally  existing  balance  or 
symbiosis  with  bacteria  of  the  B,  coli  or  B. 
lactis  aerogenes  types.  It  will  require  con- 
siderable further  study  to  determine  this  ques- 
tion. Likewise  the  relation  of  B.  infantilis  to 
the  genesis  of  infantilism  must  be  left  open. 
It  may,  however,  be  stated  with  much  con- 
fidence that  intestinal  infantilism  is  associated 
(at  least  in  some  of  the  most  extreme  cases) 
with  the  persitence  and  dominance  of  types  of 
flora  which  belong  especially  to  the  period  of 
infancy  and  the  persistent  dominance  of  which 
in  the  third,  fourth,  fifth,  sixth  and  even 
eighth  year  of  life  (as  I  have  observed  it) 
must   be   regarded   as   distinctly  pathological. 

There  are  some  features  in  the  pathology 
of  infantilism  that  remain  obscure  despite  a 
somewhat  close  study  of  the  subject.  For 
example,  I  cannot  yet  offer  a  satisfactory 
explanation   of   the   extreme   abdominal   disten- 


72  INFANTILISM 

sion  met  with  in  most  of  our  cases.  Neither 
B,  hifidus  nor  B,  infantilis  are  gas-formers. 
The  same  is  true  of  the  various  coccal  and 
cocco-bacillary  forms.  It  is  unlikely  that  any 
of  them  are  primarily  concerned  with  the 
intestinal  gas-production.  Possibly  owing  to 
slow  absorption  from  the  small  intestine  the 
carbohydrates  there  are  decomposed  by  B, 
lactis  aerogenes,  which  is  probably  present  in 
the  upper  part  of  the  small  intestine.  We 
know,  for  example,  that  when  acting  on  potato 
this  organism  forms  gas  abundantly.  But  the 
study  of  the  diarrhoeal  fecal  fields  gives  no 
suggestion  that  there  is  any  excessive  multi- 
plication of  B.  lactis  aerogenes  in  the  small 
intestine.^ 

I  find  it  impossible  at  present  to  offer  a 
well-supported  explanation  of  the  putrefactive 
cleavages  which  are  so  active  in  the  intestine. 
Which  bacteria  or  groups  of  bacteria  are 
responsible  in  this  disease  for  the  production 
of  indol,  indolacetic  acid,  phenol  and  para- 
oxyphenylacetic  acid  is  still  far  from  clear. 
Until  we  meet  with  more  success  in  getting 
B.  infantilis  and  B,  hifidus  to  grow  outside 
the  body  as  they  grow  in  the  intestinal  tract, 
we    cannot   hope    to    clear   up    this    feature    of 

^  It  must  be  remembered  that  we  have  not  had  the  opportunity 
to  study  bacteriologically  any  of  our  infantilism  patients  in  the 
stage  characterized  by  active  gas-formation  and  distension  of  the 
small  intestine. 


INFANTILISM  73 

the   pathology   of   the    affection,    and    it    seems 
best  at  present  not  to   attempt  its  discussion. 

It  has  been  shown  that  the  persistence  and 
overgrowth  of  bacterial  flora  of  the  nursling 
period  is  a  characteristic  of  the  infantilism 
patients  reported  in  this  publication.  Of  the 
conditions  leading  to  this  persistence  and  over- 
growth nothing  positive  is  known,  and  this 
necessary  knowledge  can  be  gained  only  by  very 
careful  and  extended  bacteriological  studies  of 
the  intestinal  bacteria  in  the  earliest  stages  of 
the   disease. 

The  condition  of  infantilism  which  has  been 
described  is  one  possessing  clearly  defined 
clinical  characters.  "Whether  the  bacterial  causes 
of  the  affection,  or,  more  properly,  its  bac- 
terial associations,  are  always  of  the  same 
nature  as  those  here  described  must  be  left 
an  open  question.  The  studies  which  have 
been  made  point  to  a  definite  relation  between 
the  clinical  phenomena  and  the  peculiar  bac- 
terial flora,  but  the  thoroughly  studied  cases 
have  been  few,  and  wider  experience  may 
possibly  teach  us  that  our  definite  clinical  type 
may  be  associated  with  more  than  one  group 
or   symbiotic  association  of   bacteria. 

Other  etiological  factors  than  intestinal  in- 
fection in  the  cases  of  intestinal  infantilism 
seem  improbable,  although  they  cannot  be  posi- 
tively excluded.     The  recovery  which  has  taken 


74  INFANTILISM 

place  in  Case  I,  and  in  a  still  more  striking 
degree  in  Case  II,  as  a  result  of  carefully 
planned  dietetic  and  hygienic  measures,  seems 
to  speak  against  the  specific  influence  of  non- 
intestinal  elements  of  causation,  as  for  exam- 
ple disorders  in  the  functions  of  glandular 
organs,  such  as  the  thyroid  gland  or  the  an- 
terior lobe  of  the  pituitary  body.  It  is  note- 
worthy that  in  all  our  cases  of  infantilism 
there  have  been  at  least  some  indications  of 
rickets.  Since  the  retardation  in  the  growth 
of  the  skeleton  seems  clearly  referable  to  the 
inadequate  absorption  of  calcium  and  mag- 
nesium, it  is  likely  that  such  indications  of 
rickets  as  have  been  observed  are  also  related 
to  this  defect  in  assimilation  of  the  alkali 
earths.  Our  cases  point,  however,  to  the  cor- 
rectness of  the  view  that  something  more  than 
mere  failure  to  adequately  absorb  calcium  and 
magnesium  must  enter  into  the  pathology  of 
rickets,  since  in  cases  of  such  marked  skeletal 
retardation  as  we  have  in  our  examples  of 
infantilism  there  should  have  been  the  fullest 
opportunity  for  the  development  of  rickets, 
were  this  disease  dependent  merely  on  the 
non-assimilation  of  the  bone-forming  elements. 
Under  the  circumstances  the  relative  slight- 
ness  of  the  rachitic  manifestations  is  a  feature 
of    considerable    interest. 


INFANTILISM  75 

The  Acute  and  Subacute  Infections  Leading 
TO    Infantilism 

Although  unable  to  give  an  adequate  account 
of  the  bacteriology  of  the  acute  and  subacute 
cases  of  enterocolitis  which  in  my  judgment 
are  the  antecedents  of  chronic  infantilism,  I 
wish  to  mention  here  the  existence  of  a  type 
of  intestinal  inflammation  which  stands  in  this 
causative  relation  to  the  chronic  affection. 
These  cases  usually  begin  between  the  end  of 
the  first  year  and  the  middle  of  the  third. 
They  are  characterized  by  diarrhoea  (usually 
without  tenesmus)  with  an  abundance  of  mucus, 
but  no  blood.  The  diarrhoeal  discharges  are 
usually  not  very  frequent.  The  loss  in  weight 
is  not  rapid  (1-2  ounces  daily),  but  may 
progress  until  the  child  is  much  emaciated. 
There  is  usually  considerable  flatulence.  There 
is  a  moderate  or  marked  fall  in  haemoglobin. 
The  temperature  is  normal  or  subnormal.  The 
appetite  may  be  unimpaired.  The  disease  lasts 
from  three  to  six  weeks  and  recurrences  are 
very  apt  to  occur.  The  carbohydrates  are  very 
badly  tolerated  and  many  relapses  are  cer- 
tainly due  to  their  incautious  use. 

The  urine  in  the  course  of  this  disease  gives 
intense  reactions  for  indican  and  for  aromatic 
oxyacids. 

An  examination  of  the  Gram-stained  fields 
from    the    stool    of    a   typical    example    of   this 


76  INFANTILISM 

infection  shows  it  to  consist  almost  wholly  of 
Gram-positive  bacilli  (often  lying  parallel  to 
each  other  in  groups)  presenting  the  morpho- 
logical characters  of  the  simple  form  of  B.  hifidus. 
From  the  stools  B,  hifidus  can  be  readily  cul- 
tivated and  the  same  microorganism  grows 
very  freely  in  its  bifid  forms  in  dextrose  bouil- 
lon fermentation  tubes.  B,  infantilis  is  obtain- 
able from  the  stools  of  some  cases,  perhaps  of 
all.  From  the  mucus  B,  hifidus  grows  freely, 
sometimes  almost  alone,  in  fermentation  tubes. 
It  appears  probable  that  B,  hifidus  is  very 
abundant  in  the  stools  of  these  cases,  but  it  is 
not  possible  at  present  to  say  to  what  extent 
it  makes  up  the  fecal  fields.  A  noteworthy 
feature  is  the  very  small  number  of  Gram- 
negative  bacteria  seen  in  the  fields. 

The  close  similarity  between  the  intestinal 
flora  in  this  acute  or  subacute  affection  and  in 
infantilism  makes  a  causal  relation  between  the 
former  and  the  latter  highly  probable.  Up  to 
the  present  time  I  have  had  no  opportunity  to 
observe  an  indubitable  transition  of  the  acute 
disease  into  the  chronic  one  with  the  help  of 
methods  adequate  to  establish  the  proof  of 
such  a  relation  as  that  just  suggested.  The 
methods  now  employed  were  not  known  to  us 
when  the  cases  of  infantilism  here  described 
were  in  their  subacute  stage.  On  the  other 
hand,    the   acute   or    subacute   cases   presenting 


INFANTILISM  77 

the  flora  above  mentioned  have  not  been  long 
enough  under  observation  to  determine  whether 
any  of  them  are  developing  the  extreme  and 
persistent  retardation  to  which  the  word  infan- 
tilism may  properly  be  applied. 

Mild  Types  of  Intestinal.  Infantilism 

It  seems  to  me  desirable  to  restrict  the  use 
of  the  word  infantilism  to  those  cases  of 
intestinal  origin  in  which  the  subjects  are 
strikingly  undeveloped  for  years  and  in  which 
the  absolute  arrest  of  growth  has  persisted  for 
at  least  one  year.  The  atrophic  conditions  of 
infancy  which  are  grouped  under  the  term 
marasmus  belong  in  a  different  clinical  cate- 
gory and  have,  I  believe,  a  different  genesis. 
There  are,  however,  instances  of  a  moderate 
retardation  in  growth  (not  necessarily  with 
actual  arrest  in  development)  which  appear  to 
be  mild  types  of  the  condition  which  has  been 
described  in  this  study  only  in  its  extreme 
examples.  B.  hifidus  appears  to  be  less  abun- 
dantly present  in  these  milder  cases,  in  which 
various  coccal  forms  may  be  prominent  and  in 
which  Gram-negative  forms  (representing  B.  coli) 
are  probably  seldom  lacking.  No  serious  attempt 
has  yet  been  made  to  study  these  mild  forms 
of  arrested  growth  of  intestinal  origin,  but 
there  is  reason  to  think  that  at  least  some  of 


78  INFANTILISM 

these  cases  are  allied  to  the  severer  type  both 
in  etiology  and  pathology. 

The   Sequelae  ai!Td   Peognosis  of   Intestinal 

Infantilism 
I    have    not    at    command    the    data    from    a 
sufficient  number  of  instances  of  infantilism  to 
permit   even   an  approach   to   generalization  as 
to  the  outcome  of  the  disease.     Only  the  patient 
study  of  many  cases  through  extended  periods 
of  time   and  under   well  understood   conditions 
will  yield  the  facts  necessary  for  safe  general- 
ization.    Nevertheless    there    are    some    obvious 
commentaries    which    are    justified    by    limited 
experience.     Of  these   by   far  the  most  impor- 
tant   is    that    in    general    the    outlook    is    very 
largely   determined   by   the   nature  of  the   care 
which   the   patient   can   obtain.    Neglect   means 
deterioration  into  a  state  of  extreme  involution, 
ending     either     in     death     (from     intercurrent 
disease  or  exhaustion)   or  in  a  relatively  fixed 
state  of  under-development  little  ameliorated  by 
any   course  of  treatment   at  present  known  to 
us.    Intelligent   and   careful   treatment,    on   the 
other  hand,   leads  to   at  least    some  degree  of 
improvement    and   perhaps    to   a   very    striking 
betterment   in   nutrition   and  growth.    Whether 
a  child  whose  arrest  of  growth  has  lasted  for 
five  years,  leaving  him  at  the  end  of  that  time 
50  per  cent,  below  the  average  weight  for  this 


INFANTILISM  79 

age,  can  under  any  conditions  be  expected  to 
develop  into  a  man  of  average  size,  I  am 
unable  to  say.  That  our  methods  of  treating 
such  cases  fall  short  of  the  ideal  is  not  im- 
probable, and  it  may  be  that  in  children  with 
extreme  but  uncomplicated  infantilism  the  out- 
look for  progress  toward  normal  development 
would  be  considerably  better  than  we  can  at 
present  assert  it  to  be,  assuming  that  further 
improved  methods   should   come   into   use. 

From  the  cases  observed  by  Dr.  Holt  and 
myself  we  have  been  instructed  in  several 
particulars  relating  to  sequelae  and  complica- 
tions. Case  V  of  our  group  developed  a  high 
grade  of  simple  anaemia  which  lasted  several 
years;  yet  after  so  lasting  the  child  began  to 
grow  in  a  promising  manner  despite  the  fact 
that  the  anaemia  still  persists.  The  fact  is 
instructive  as  pointing  to  a  dissociation  of  the 
causes  of  the  anaemia  and  the  causes  of  the 
retarded  growth.  No  opinion  can  be  ventured 
as  to  the  ultimate  influence  of  the  anaemic 
state  on  the  prognosis.  In  Case  IV  there  was 
an  early  and  marked  anaemia,  but  this  did 
not  persist  for  more  than  a  year,  and  as  the 
nutritional  conditions  improved  the  haemoglobin 
rose  from  35  to  61  per  cent.  In  Case  III 
anaemia  was  only  moderate,  and  during  the 
past  two  years  there  has  been  a  gradual  and 
fairly    satisfactory    growth    of    the    body.    In 


80  INFANTILISM 

Case  II  the  improvement  was  very  slow 
through  many  years,  but  recently  has  become 
remarkably  rapid.  With  this  rapid  improve- 
ment in  growth  some  errors  were  made  in 
diet  owing  to  a  desire  to  push  the  gain  by 
full  feeding.  This  experiment  resulted  disas- 
trously in  that  it  was  soon  followed  by  grand 
mal  epileptiform  seizures,  coming  at  short 
intervals.  Two  years  previous  to  this  out- 
break the  child  had  had  a  few  short  seizures 
of  loss  of  consciousness  without  motor  symp- 
toms, and  it  now  appears  that  these  were 
probably  examples  of  petit  mal.  The  onset  of 
grand  mal  seizures  was  attended  here  by  a 
very  considerable  rise  in  the  indications  of 
intestinal  putrefaction.  I  believe  this  case  to 
be  a  clearly  defined  and  unimpeachable  instance 
of  epilepsy  developing  as  the  result  of  cerebral 
irritative  intoxication  from  putrefactive  prod- 
ucts absorbed  from  the  intestine.  I  have  long 
maintained  that  such  cases  occasionally  arise, 
but  it  is  seldom  that  the  antecedent  conditions 
are  so  well  known  to  the  physician  as  in  this 
case.  This  case  is  thus  in  my  judgment  a 
singularly  definite  example  of  epilepsy  arising 
from  intestinal  intoxication  in  a  child  with  a 
nervous  system  rendered  unstable  by  long  intox- 
ication of  milder  intensity  than  that  needed  to 
induce  grand  mal  seizures.  In  this  instance  a 
rapid  improvement  set  in  with  the  institution 


INFANTILISM  81 

of  very  careful  regulation  of  diet  and  environ- 
ment, but  the  ultimate  outcome  of  the  epilepti- 
form state  cannot  be  predicted. 

The    Theeapeutic    Modification    of    the    Bac- 
TEKiAL.  Conditions  in  Intestinal  Infantilism 

The  central  aim  in  the  treatment  of  in- 
fantilism is  the  modification  of  the  bacterial 
flora  of  the  intestine.  There  is  no  evidence 
that  any  therapeutic  measures  which  do  not 
exert  some  direct  or  indirect  influence  in  this 
direction  can  be  truly  effective.  To  bring 
about  an  amelioration  of  the  bacterial  condi- 
tions in  the  intestine  is  a  task  of  the  utmost 
difficulty,  calling  for  an  understanding  of 
principles,  close  attention  to  details,  and  pains- 
taking care  during  a  long  period  of  time.  In 
some  important  aspects  there  is  a  close  similarity 
between  the  therapeutic  requirements  of  intes- 
tinal infantilism  and  those  of  the  extreme 
forms  of  chronic  saccharo-butyric  putrefaction 
associated  with  an  infection  by  bacteria  of  the 
B.  perfringens  and  streptococcus  types.  In 
both  we  have  to  deal  with  a  chronic  entero- 
colitis leading  to  failure  in  nutrition;  in  both 
the  element  of  intoxication  is  prominent,  and 
in  both  apparently  trivial  errors  in  diet  are 
followed  by  temporary  setbacks.  There  are, 
however,  two  highly  significant  differences  be- 
tween   these    types    of    infection,    and   both    of 

6 


82  INFANTILISM 

these  differences  make  for  a  more  favorable 
outlook  in  the  case  of  the  disease  of  childhood 
— at  least  so  far  as  the  prospect  of  life  is 
concerned.  One  of  these  differences  lies  in 
the  nature  of  the  pathological  process,  the 
other  in  the  circumstances  attendant  on  child- 
hood. The  process  in  extreme  saccharo-butyric 
putrefaction  is  one  of  very  long  standing,  and 
probably  leads  to  an  impairment  in  the  ability 
of  the  mucosa  to  regenerate  adequately  the 
excessively  desquamated  epithelium;  it  is  ques- 
tionable whether  in  infantilism  the  damage  to 
the  mucosa  is  ever  so  profound  as  this.  And 
as  regards  the  attendant  circumstances  of 
childhood  there  is  the  essential  fact  that  the 
patient's  age  makes  it  possible  to  control  with 
precision  the  conditions  of  his  life,  whereas  in 
the  extreme  saccharo-butyric  infections  of  adults 
the  freedom  of  action  possessed  by  the  indi- 
vidual sooner  or  later  leads  him  to  make  mis- 
takes in  his  habits  of  life  which  lead  to  dangerous 
relapses  and  ultimately  to  death. 

What  I  shall  here  write  about  the  treatment 
of  infantilism  is  based  on  the  study  of  only 
a  small  number  of  patients,  and  for  this 
reason,  if  for  no  other,  will  be  incomplete. 
This,  however,  does  not  deter  me  from  offer- 
ing some  definite  advice  in  regard  to  treat- 
ment, for  I  believe  that  the  experience  gained 
from  the  highly  detailed  study  of  a  few  patients 


INFANTILISM  83 

will  prove  useful  in  the  handling  of  this  not 
very  uncommon  condition,  by  those  whose 
opportunities  for  study  have  been  less  good 
than  mine.  I  shall  arrange  what  I  have  to 
say  under  the   following  headings: 

General  Hygienic   Measures. 

Dietetic   Measures. 

Pharmacological    Measures. 

Genekal  Hygienic  Measures 
In  the  care  of  the  subjects  of  infantilism  the 
hygiene  of  environment  is  of  much  importance 
in  reinforcing  the  effects  of  more  specific 
therapeutic  measures.  Two  environmental  re- 
quirements stand  out  sharply  and  require  the 
consideration  of  the  physician;  first,  a  tem- 
perate, equable  and  fairly  sunny  climate,  and, 
secondly,  soothing  human  surroundings  and 
limited  companionship.  In  all  marked  states 
of  infantilism  the  circulation  is  impaired  and 
the  loss  of  animal  heat  is  a  severe  tax  to  the 
organism  if  there  be  prolonged  exposure  to 
cold.  In  Case  II  the  cold  months  of  winter 
were  spent  in  a  mild  climate,  which  made  it 
possible  to  be  out  of  doors  a  large  part  of 
the  day  without  excessive  radiation  of  heat, 
and  there  is  good  reason  to  think  this  pre- 
caution was  a  material  help  in  paving  the  way 
for  the  subsequent  improvement  in  nutrition. 
In    Case   I   it    was    impracticable   to    send    the 


84  INFANTILISM 

child  to  a  warm  climate  in  winter,  and  the 
exposure  to  the  winter's  cold  in  New  York 
seemed  clearly  an  obstacle  to  quick  improve- 
ment in  nutrition.  Except  on  the  most  in- 
clement days  the  child  should  be  out  of  doors 
for  a  time  despite  the  drain  on  animal  heat, 
for  the  alternative  of  remaining  indoors  is 
still  more  objectionable.  It  is  especially  in  the 
sununer  months  that  these  children  tend  to  do 
badly.  This  is  probably  attributable  mainly  to 
the  difficulty  in  securing  food  sufficiently  free 
from  objectionable  bacteria  during  the  hot 
months,  but  is  doubtless  due  in  part  to  the 
prostrating  effects  of  prolonged  exposure  to  a 
high  temperature.  By  taking  great  care  it  is 
possible  to  avoid  these  common  summer  dis- 
turbances of  digestion  connected  with  hot 
weather,  and  this  is  in  itself  a  very  important 
advantage.  Even  in  selecting  a  mild  winter 
climate  it  is  necessary  to  balance  the  advan- 
tages of  mild  weather  against  the  dangers  that 
arise  from  the  inability  to  secure  clean  food. 

It  is  essential  that  the  attendant  should  be 
a  person  of  more  than  ordinary  tact,  gentle- 
ness, good  sense,  patience  and  cheerfulness, 
for  the  subject  of  infantilism  is  often  irritable, 
peevish  and  emotionally  depressed  and  depress- 
ing. The  patient  should  see  visitors  only 
seldom  and  only  for  a  few  minutes  at  a  time. 
If   permitted  to   play   with    other    children    he 


INFANTILISM  85 

should  be  with  only  one  child  at  a  time.     The 
intoxication    leads    to    so    much    physical    and 
mental  languor  that  it  is  inadvisable  to  attempt 
to   teach   these  children   in   the   ordinary   ways. 
They    can   only   be   coaxed,    very   tactfully   and 
cautiously,  into   an  interest  in  numbers,  letters 
and    objects     of    various     colors    and     shapes. 
Prolonged    attention    is    undesirable    and    leads 
to    extreme    fatigue.     These    children    are    des- 
tined to  be  much  retarded  in  the   acquirement 
of  knowledge,  but  as  their  natural  intelligence 
is    not    distinctly    impaired    they    can    develop 
satisfactorily  in   a  few  directions.     The  illness 
of    these   unfortunate    children    is    not    without 
the    compensation   that   they   cannot    be    forced 
into  the   stupid  conventional  pleasures   so  com- 
monly  provided  for   children.     To   this   and   to 
the  opportunity  for   quiet   reflection  I  am  dis- 
posed to  attribute  the  noticeable  thoughtfulness 
of  most  of  the  subjects  of  infantilism.    When 
the  stage   has  been  reached  in  which   there  is 
a  steady  gain  in  weight,  the  periods  of  teach- 
ing can  be  increased.    I  believe  that  the  ulti- 
mate mental  growth  of   these  children  will  be 
good    in    cases    that    are    carefully    managed. 
One    patient    of    extreme    type    whom    I   have 
had  under  observation  from  time   to   time  for 
ten  years  is  now  married  and  in  good  health. 
She  is  a  well   educated  and  cultivated  person, 
but   undersized. 


86  INFANTILISM 

The  patients  must  be  encouraged  to  take 
exercise  daily,  even  if  it  causes  fatigue.  In 
experiments  which  I  made  on  healthy  young 
men  who  were  intoxicated  experimentally  with 
indol,  it  was  found  that  active  exercise  dis- 
tinctly aided  the  subjects  in  overcoming  the 
sense  of  great  fatigue  from  which  they  suf- 
fered. This  is  probably  to  be  attributed  to 
the  improved  opportunity  for  oxidation  which 
exercise  affords.  I  have  noticed  the  same 
effect  of  exercise  on  several  adults  with  pre- 
sumably indolic  intoxication.  But  it  is  easy 
to  overdo  in  exercise  for  these  retarded  chil- 
dren, and  it  is  important  to  avoid  excessive 
fatigue  as  it  apparently  acts  unfavorably  on 
the    digestive    processes. 

Dietetic  Measuees 
Dietetic  measures  are  the  keystone  of  the 
therapeutic  arch  in  infantilism.  Without  the 
closest  attention  to  them  there  is  little  chance 
of  beneficially  modifying  the  intestinal  pro- 
cesses which  underlie  the  affection.  Cautious 
and  prolonged  experimentation  is  necessary  to 
obtain  the  best  dietetic  conditions  for  each 
patient.  The  problem  varies  somewhat  in  dif- 
ferent individuals  and  may  vary  for  the  same 
patient  from  time  to  time.  It  may  be  stated 
in  the  following  general  terms:  to  secure  the 
absorption    of    foodstuffs    adequate    in    quality 


INFANTILISM  87 

and  quantity  for  the  reasonably  rapid  growth 
of  skeleton,  muscles,  blood  and  nervous  sys- 
tem, with  as  little  waste  as  possible  from  non- 
absorption  and  as  little  opportunity  as  possible 
for  excessive  putrefaction.  If  the  absorption 
of  foodstuffs  be  indeed  adequate  for  the  growth 
of  bones,  muscles  and  nervous  system  it  is 
probable  that  it  will  suffice  also  for  the  growth 
of  viscera  and  the  production  of  sufficient  fat. 
It  is  necessary  to  discuss  separately  the  dif- 
ferent types  of  foodstuffs  in  their  relation  to 
infantilism  before  considering  any  special  diet- 
ary as  a  whole. 

The  Carbohydrates,  It  has  been  already 
mentioned  that  the  carbohydrates  are  the 
obvious  and  fruitful  cause  of  derangements  of 
digestion  that  are  clinically  determinable,  espe- 
cially diarrhoea  and  flatulence.  Probably  by 
far  the  greater  number  of  acute  disturbances 
of  digestion  in  the  course  of  infantilism  are 
referable  to  errors  relating  to  the  carbohy- 
drates. I  deem  it  impossible  at  present  to 
speak  with  precision  and  fulness  regarding  the 
relative  merits  and  demerits  of  the  various 
carbohydrate  foods  with  respect  to  infantilism. 
From  a  considerable,  but  by  no  means  ex- 
haustive, experience  with  various  carbohydrate 
foods  I  have  reached  the  conclusion  that  such 
carbohydrate  food  as  can  be  taken  by  these 
patients   is   best  given  in  the   form   of   starch- 


88  INFANTILISM 

holding  preparations,  and  not  in  any  ordinary 
form  of  sugar.  I  have  seen  the  best  results 
from  the  use  of  well-boiled  rice  or  arrow- 
root or  cream  of  wheat,  supplemented  with  a 
partly  dextrinized  preparation  such  as  the 
Huntley  and  Palmer  breakfast  biscuits.  Milk 
sugar,  in  the  proportions  in  which  it  occurs  in 
milk,  may  also  be  well  taken,  especially  when 
a  distinct  improvement  in  nutrition  is  already 
in  progress.  I  suspect  that  milk  sugar  is 
better  tolerated  than  an  isodynamic  quantity 
of  glucose  or  saccharose,  but  have  no  proof 
that  this  is  so.  Foods  which  contain  an  abun- 
dance of  soluble  carbohydrates,  as  Mellin's 
food  or  malted  milk,  cannot  be  recommended. 
Perhaps  the  most  objectionable  of  all  ordinary 
natural  carbohydrate  foods  is  potato,  which 
can  generally  be  counted  on  to  occasion  flatu- 
lence. The  reason  for  this  is  not  at  present 
clear.  In  the  severest  forms  of  infantilism 
the  total  quantity  of  carbohydrates  which  can 
be  tolerated  may  be  very  small,  and  it  may 
be  possible  to  supply  less  than  one  fifth  of 
the  calories  required  by  the  organism  (instead 
of  nearly  one  half  as  in  health)  in  this  way. 
An  especial  sensitiveness  to  carbohydrates  may 
be  developed  during  febrile  attacks  (as  those 
due  to  taking  cold),  and  it  is  then  best  to 
withdraw  them  entirely  for  a  few  days. 


INFANTILISM  89 

In  every  case  of  infantilism  one  of  the  most 
important  and  difficult  tasks  for  the  physician 
is  to  determine  how  much  carbohydrate  food 
his  patient  can  utilize  at  a  given  time.  The 
amount  which  is  appropriate  at  one  time  may 
be  less  or  more  than  can  be  tolerated  at 
another.  Where  the  patient  can  take  a  small 
quantity  of  carbohydrates  it  seems  best  to 
give  it  divided  in  the  several  kinds.  Thus  at 
one  time  in  the  day  the  child  receives  a 
Huntley  and  Palmer  breakfast  biscuit  with 
minced  beef  or  chicken  or  with  beef  juice;  at 
another  time  he  receives  a  portion  of  boiled 
rice  with  one  or  two  ounces  of  milk,  and  at 
still  another  time  he  receives  a  larger  portion 
of  milk  alone.  It  is  unwise  to  concentrate  the 
carbohydrates  at  one  period;  thus  milk,  rice 
and  biscuit  should  not  be  given  at  one  meal. 
If  the  allotted  carbohydrates  appear  to  be  well 
tolerated  (i.e,  cause  little  or  no  flatulence,  no 
marked  softening  of  the  stools,  no  increase  of 
mucus  and  no  increase  of  indican  in  the  urine) 
it  may  be  cautiously  increased  in  amount.  If 
the  child  has  been  receiving  twenty  grams  of 
boiled  rice  at  a  feeding,  the  amount  should  be 
increased  by  five  grams  rather  than  by  ten 
grams  until  a  point  is  reached  at  which  it 
appears,  after  a  trial  of  several  days,  that  the 
increased  amount  is  not  well  tolerated  (i.e. 
causes    flatulence    or    abdominal    discomfort   or 


90  INFANTILISM 

slight  diarrhoea  or  increase  of  indican).  It 
may  then  be  necessary  to  fall  back  to  the 
original  amount  of  rice,  or  it  may  be  that  a 
portion  of  the  attempted  increase  can  be  main- 
tained  with   advantage.^ 

In  every  experiment  made  with  a  view  to 
establishing  a  diet  the  following  cardinal  rnle 
should  be  observed:  the  physician  should  vary 
only  one  article  of  diet  at  a  time.  If  more 
than  one  article  of  diet  be  varied  at  once  the 
experiment  will  lack  scientific  precision  and 
the  best  results  cannot  be  attained.  When  a 
tentative  diet  is  tried  it  should  be  so  made 
up  as  to  permit  a  definite  gain  in  knowledge 
from  intelligent  successive  variations  in  the 
amounts  of  the  various  foodstuffs  employed. 
This  careful  and  painstaking  experimentation 
calls  for  much  patience,  but  is  rewarded  by 
the  fact  that  it  leads  to  a  gain  in  definite 
information.    Haphazard,    quick    variations    of 

^I  have  made  a  fe-w  observations  on  the  use  of  diastatic  fer- 
ments as  an  aid  in  the  digestion  of  carbohydrates,  but  such 
experience  as  I  have  had  has  been  too  unsystematic  to  permit  any 
definite  inferences  as  to  the  value  of  such  enzymes.  I  doubt  very 
much  if  their  use  materially  influences  the  course  of  the  affection 
or  makes  it  possible  to  increase  the  carbohydrate  food  more  rapidly 
than  would  otherwise  be  the  case.  This  latter  point,  which  is  one 
of  considerable  practical  importance,  must  be  settled  by  well- 
planned  experimental  methods.  In  the  meantime  I  think  it  well 
to  give  the  patient  the  benefit  of  the  doubt  by  employing  small 
quantities  of  an  active  diastatic  ferment,  prepared  in  the  dry 
form,  as,  for  example,  taka- diastase.  The  powder  should  be  well 
mixed  with  the  food  at  body  temperature. 


INFANTILISM  91 

several  factors  simultaneously  may  accidentally 
give  good  results  at  times;  yet  in  the  long 
run  there  is  a  saving  of  time,  for  all  con- 
cerned, if  the  physician  takes  the  trouble  to 
proceed  more  deliberately  with  the  establish- 
ment of  the   dietetic  treatment. 

The  Fats,  The  intestinal  infections  asso- 
ciated with  infantilism  call  for  the  most  care- 
ful regulation  of  the  fat  intake.  This  intake 
cannot  be  prescribed  in  any  fixed  and  special 
terms,  but  only  on  the  basis  of  a  general 
principle.  The  principle  to  be  obeyed  is  the 
following:  give  only  so  much  fat  as  will  in 
large  measure  be  resorbed.  The  stools  should 
not  be  permitted  to  continue  voluminous  and 
excessively  fatty.  The  objections  to  this  con- 
tinual fat  loss  are  mainly  two — the  unnecessary 
and  harmful  loss  of  calcium  and  magnesium 
soaps  and  the  interference  with  digestion  and 
absorption  which  is  occasioned  by  the  presence 
of  fatty  material,  the  latter  tending  to  favor 
intestinal  putrefaction.  From  the  fact  that  cal- 
cium and  magnesium  are  constantly  lost  as 
soaps  it  does  not  necessarily  follow  that  if  we 
prevent  the  alkali  earth  metals  from  being 
saponified  we  shall  prevent  them  from  being 
lost  in  the  feces.  We  are  still  too  ignorant 
of  the  conditions  under  which  these  elements 
are  absorbed  to  form  a  judgment  on  this  point. 
If   we   may    judge    from    the    case    of   healthy 


92  INFANTILISM 

children  already  cited,  it  is  not  unfair  to 
assume  that  positive  balances  in  calcium  and 
magnesium  are  more  likely  to  be  attained  by 
the  reduction  of  the  milk  fat  than  through 
permitting  the  free  use  of  milk  fat.  While  I 
am  not  sure  that  we  are  justified  in  trans- 
ferring these  results  on  nearly  healthy  infants 
to  the  absorption  in  our  cases  of  infantilism, 
it  is  obvious  that  at  least  there  is  a  possibility 
of  securing  improved  absorption  if  we  check 
the  persistent  loss  of  soaps  with  the  stools. 
Much  more  study  is  necessary  to  show  us 
whether  the  alkali  earth  metals  are  normally 
absorbed  in  an  important  degree  as  soaps  of 
these  elements.  Probably  this  is  one  of  the 
most  important  ways  of  absorption  for  these 
metals  and  we  should  strive  not  to  prevent 
saponification  but  to  secure  good  soap  absorption. 
In  any  case  of  infantilism  in  which  there  is 
a  continuous  excessive  loss  of  fat,  the  intake 
of  fatty  food  should  be  gradually  lowered 
until  the  feces  no  longer  show  the  indications 
of  such  loss.  When  the  level  has  been  reached 
at  which  the  movements  are  no  longer  homo- 
geneous, but  are  made  up  of  a  conglomerate 
of  small  individual  masses,  the  fat  loss  will 
not  be  excessive.  From  time  to  time  the  fat 
may  be  somewhat  increased,  for  if  the  progress 
of   the   affection   is   favorable   there  will   be   a 


INFANTILISM  93 

gradual    increase    in    the    power    of    absorbing 
fat. 

In  Case  I  the  relation  between  the  intake 
of  fat  and  the  loss  of  fat  in  the  feces  was 
carefully  determined  by  Dr.  Wakeman  for  a 
period  of  eleven  days,  during  which  there 
existed  an  insignificant  positive  calcium  bal- 
ance, a  very  small  retention  of  nitrogen  and 
an  essentially  stationary  weight.  The  daily 
intake  of  fat  (neutral  fats,  fatty  acids  and 
soaps)  amounted  to  38.28  grams,  the  intake 
for  the  period  having  been  382.8  grams.^  Dur- 
ing the  same  period  there  was  a  daily  loss  of 
fats  equal  to  5.56  grams,  or  55.6  grams  for 
the  period.  The  fat  loss  is  here  equivalent  to 
14.5  per  cent,  of  the  ingested  fat.  This  is  dis- 
tinctly in  excess  of  the  normal  fat  loss,  but 
does  not  represent  extremely  low  fat  absorp- 
tion. The  fat  excess  was  sufficient  to  prevent 
the  conglomeration  of  the  feces.  Two  months 
before  this  period  the  absorption  of  fat  was 
much  less  good  with  the  same  fat  intake,  for 
it  reached  at  this  time  as  high  as  22  per  cent., 
and    even    25    per    cent.,    of    the    ingested    fat. 

*  These  fats  were  distributed  as  follows : 

Neutral  fats   66.55  per  cent. 

Fatty  acids  16.49  per  cent. 

Soaps    16.96  per  cent. 

The  figure  here  given  for  soaps  is  doubtless  too  high,  as  other 
substances  than  fat  must  have  found  their  way  into  the  ether 
extract. 


94  INFANTILISM 

The  fat  loss  was  even  larger  tlian  this  at  the 
time  when  the  patient  first  came  nnder  ob- 
servation, and  on  several  subsequent  occasions. 
On  these  occasions  the  fat  intake  was  decreased 
to  meet  the  poor  absorption.  Although  the 
fat  loss  was  as  great  as  14.2  per  cent,  so 
recently  as  three  months  ago,  in  Case  I,  I  did 
not  at  this  time  make  any  further  reduction 
in  fat,  as  there  was  evidence  of  a  slowly  in- 
creasing power  of  absorption.  Eecently  (June  1, 
1908)  I  deemed  it  best  to  reduce  the  fat  to 
25  grams  daily,  and  on  this  basis  an  entirely 
satisfactory  absorption  was  secured.  It  should 
be  noted  that  the  relatively  good  fat  absorp- 
tion of  recent  periods  in  this  patient  does  not 
represent  the  actual  state  of  absorption  until 
a  period  of  general  symptomatic  improvement 
(without  considerable  gain  in  weight,  though 
a  forerunner  to   such  gain)   had  set  in. 

The  Proteins.  On  the  use  of  the  proteins 
in  infantilism  I  have  not  as  yet  been  able  to 
obtain  much  specific  information,  as  oppor- 
tunities for  thorough  investigation  of  the  effects 
of  different  types  of  proteins  have  been  in- 
adequate. In  children  under  three  years  of 
age  it  is  probably  good  practice  to  give  the 
greater  part  if  not  all  the  proteins  of  the 
food  as  milk  proteins.  The  conditions  of 
digestion  are  apt  to  be  such  in  infantilism 
that  eggs  are  not  well  tolerated,  but  there  is 


INFANTILISM  95 

no  evidence  that  this  is  due  to  an  intolerance 
of  egg  albumin,  but  rather  that  it  is  due  to 
an  intolerance  for  the  constituents  of  the  yolk. 
The  question  of  the  use  of  meat  is  one  that 
comes  up  in  every  case  in  children  over  three 
years  of  age.  In  Cases  I  and  II  small  quan- 
tities of  meat  were  permitted  during  long 
periods  of  time  as  part  of  the  protein  food. 
There  was  no  evidence  of  any  detrimental 
effects  from  the  cautious  use  of  meat.  On  the 
other  hand,  there  is  also  no  positive  evidence 
that  the  use  of  meat  might  not  have  been 
dispensed  with,  through  the  substitution  of 
milk  proteins.  I  have  not  been  able  to  satisfy 
myself  either  in  Case  I  or  Case  II  that  the 
cautious  use  of  minced  beef  or  minced  chicken 
once  daily  has  tended  to  cause  greater  putre- 
factive decomposition  than  was  the  case  where 
milk  proteins  alone  were  used.  But  in  both 
these  cases  there  were  periods  when  meat 
was  allowed  in  excessive  amounts,  as  indicated 
by  symptoms  of  intoxication  and  unnecessarily 
abundant  putrefactive  products  in  the  urine. 
A  consideration  which  has  had  some  influence 
in  determining  the  use  of  meat  has  been  the 
presence  of  iron  in  such  food.  The  dietary 
in  cases  of  infantilism  tends  to  be  low  in  iron 
and  it  has  seemed  desirable  to  make  use  of 
some  meat  rather  than  to  use  milk  as  the 
exclusive    source   of   protein,   but   whether    this 


96  INFANTILISM 

has  really  been  effective  in  helping  to  over- 
come the  anaemia  nearly  always  present,  it  is 
impossible  to  say. 

It  has  already  been  mentioned  that  the 
physician  tends  in  the  treatment  of  infantilism 
to  give  an  excess  of  protein  owing  mainly  to 
the  difficulty  in  giving  an  adequate  quantity  of 
carbohydrates  and  fats.  I  have  myself  tended 
to  make  use  of  a  greater  quantity  of  protein 
food  than  has  perhaps  been  wise.  The  tend- 
ency to  give  protein  in  relative  excess  was 
constantly  noted  in  both  Case  I  and  Case  II. 
It  is  only  latterly  that  I  have  learned  to  re- 
place in  a  measure  the  typical  protein  foods 
by  the  least  objectionable  form  of  protein — 
namely   gelatin. 

The  Use  of  Gelatin,  The  use  of  gelatin  as 
a  foodstuff  in  bacterial  infections  of  the  intes- 
tinal tract  has  never  received  the  attention  it 
deserves.  The  physician  is  not  infrequently 
confronted  with  a  dietetic  problem  which  con- 
sists in  endeavoring  to  maintain  nutrition  under 
conditions  where  no  combination  of  the  ordi- 
nary proteins  with  fats  and  carbohydrates 
suffices  to  maintain  a  fair  state  of  nutrition. 
The  difficulty  which  most  frequently  arises  is 
that  every  attempt  to  use  carbohydrate  food 
is  followed  by  fermentative  disturbances  of  an 
acute  or  subacute  nature  which  delay  recovery 
or    even    favor    an    existing    infection    to    the 


INFANTILISM  97 

point  of  threatening  life.  The  attempt  to 
replace  the  carbohydrates  in  large  degree  by 
proteins  is  blocked  by  the  serious  difficulty 
that  all  the  ordinary  proteins,  when  given  in 
amounts  distinctly  in  excess  of  the  habitual 
quantities,  afford  material  for  putrefactive  de- 
compositions which  it  is  necessary  to  restrict. 
A  great  desideratum,  therefore,  is  a  food 
which,  while  readily  undergoing  absorption, 
shall  furnish  a  supply  of  caloric  energy  and 
which  at  the  same  time  shall  be  exempt  from 
ordinary  fermentative  decomposition.  Such  a 
food   exists  in   gelatin. 

The  exact  nature  of  all  the  cleavage  prod- 
ucts of  gelatin  is  not  at  present  known.^  Cer- 
tain facts,  however,  stand  out  significantly. 
One  is  that  gelatin  contains  no  tryptophan 
nucleus    and    that    it    can    hence    yield    neither 

*  The  following  figures  (representing  percentages)  have  been 
obtained  for  the  composition  of  gelatin: 

Glycocoll  16.5      Glutaminic  acid  0.88 

Alanin    0.8      Aspartic  acid 0.56 

Aminovaleric  acid 1.0      Serin 0.4 

Leucin   2.1      Lysin    2.75 

Prolin 5.2      Arginin    7.62 

Phenylalanin 0.4      Histidin   0.40 

These  figures  have  been  obtained  by  Emil  Fischer,  P.  A.  Levene 
and  E.  H.  Aders:  Ueber  die  Hydrolyse  des  Leims.  Zeitschr.  f. 
physiol.  Chemie,  XXXV,  p.  70,  1902.  See  also  Emil  Fischer  and 
E.  Abderhalden:  Notizen  iiber  die  Hydrolyse  von  Proteinstoffen, 
Zeitschr.  f.  physiol.  Chemie,  XLII,  p.  540,  1904. 

The  absence  of  cystin  from  gelatin  is  noteworthy,  though  it  is 
doubtful  if  it  Dossesses  any  bearing  on  its  use   in   the  present 
connection. 
7 


98  INFANTILISM 

indol  nor  skatol  nor  indolacetic  acid  nor  indol- 
propionic  acid.  This  fact  makes  it  evident  that 
no  decomposition  of  gelatin  that  can  occur 
within  the  intestinal  tract  can  directly  con- 
tribute to  an  intoxication  in  which  the  fore- 
going substances  are  concerned.  A  second 
peculiarity  of  almost  equal  importance  is  the 
fact  that  gelatin  contains  no  tyro  sin  nucleus, 
even  the  relatively  impure  gelatin  which  is 
sold  for  cooking  purposes  giving  only  a  slight 
and  questionable  reaction  with  Millon's  reagent. 
The  absence  of  the  tyro  sin  nucleus  in  gelatin 
renders  it  impossible  for  paraoxyphenylacetic 
acid  or  paraoxyphenylpropionic  acid  to  be  formed 
in  the  course  of  bacterial  decomposition  of 
gelatin.  In  many  chronic  bacterial  infections 
of  the  digestive  tract  paraoxyphenylacetic  acid 
finds  its  way  into  the  urine  in  excessive  amounts. 
Similarly  phenol  arises  in  large  part,  perhaps 
exclusively,  from  the  decomposition  of  tyro  sin 
in  the  intestinal  tract.  It  is  thus  evident  that 
in  any  case  of  infantilism  in  which  there  is 
the  usual  evidence  of  excessive  putrefaction, 
gelatin  may  be  employed  as  a  food  without 
incurring  any  risk  of  increasing  intestinal 
putrefaction  in  the  directions   just  mentioned. 

While  gelatin  does  not  contain  either  the 
tryptophan  nucleus  or  the  tyro  sin  nucleus,  it 
gives  a  considerable  yield  of  phenylalanin.  It 
is   possible  that   through   oxidation  of   phenyl- 


INFANTILISM  99 

alanin  in  the  body  phenolic  derivatives  may- 
be produced  in  slight  amount  (through  hydrox- 
ilation  of  the  aromatic  nucleus),  but  the  facts 
at  the  present  time  known  relating  to  this 
point  are  opposed  to  this  view. 

Among  the  most  important  cleavage  products 
of  gelatin  is  glycocoll  or  amidoacetic  acid.  It 
has  been  recovered  to  the  extent  of  16%  per 
cent,  of  the  original  gelatin.  Alanin  is  present 
in  considerably  smaller  quantities.  Leucin  is 
also  a  not  unimj^ortant  cleavage  product. 
These  monamino  acids,  together  with  the 
diamino  acids,  go  to  furnish  a  large  part  of 
the  caloric  value  of  gelatin.  In  this  respect 
gelatin  resembles  other  proteids.  I  do  not 
know  whether  entirely  satisfactory  studies  have 
been  made  of  the  caloric  potential  of  gelatin 
furnished  to  the  human  body,  but  it  may 
probably  be  regarded  as  not  very  different 
from  that  of  protein  in  general,  namely  about 
4.3  calories  for  one  gram  of  gelatin.  Assum- 
ing that  the  caloric  value  of  gelatin  is  about 
four  calories  per  gram,  it  is  seen  that  30 
grams  of  gelatin  (about  1  ounce)  will  yield 
the  organism  in  the  neighborhood  of  120 
calories.  An  ounce  of  gelatin  can  be  taken 
without  difficulty  in  24  hours  in  the  food  of 
any  child  weighing  not  less  than  28  to  30 
pounds.  This  quantity  of  gelatin  cannot,  of 
course,  be  given  at  one  meal,   but  may  be  so 


100  INFANTILISM 

scattered  through  the  feedings  for  the  day  as 
to  be  easily  introduced.  It  is  obvious,  how- 
ever, that  if  owing  to  the  practically  complete 
resorption  of  this  quantity  of  gelatin,  a  child 
receives  120  calories,  this  is  an  extremely  im- 
portant contribution  to  the  entire  caloric  energy 
of  the  organism,  since  it  may  amount  to  from 
10  to  12  or  even  15  per  cent,  of  the  total  re- 
quirements of  the  organism.  It  requires  no 
argument  to  show  that  the  difference  between 
a  child's  being  able  to  avail  itself  of  30  grams 
of  gelatin  daily  and  not  being  able  to  avail 
itself  of  it  may  make  extremely  important 
differences  in  its  nutritional  record.  In  younger 
children — children  one  or  two  years  of  age — 
smaller  quantities  of  gelatin  may  advantageously 
be  employed.  It  is  not  difficult  to  introduce 
from  10  to  15  grams  daily  of  Cox's  gelatin^ 
into  the  milk  or  fermented  milk  of  a  child 
suffering   from   an   acute   intestinal   infection. 

On  the  theoretical  basis  which  has  just  been 
brought  out,  we  should  expect  to  obtain  cer- 
tain results  in  practice.  We  may  stop  for  a 
moment  to  inquire  to  what  extent  the  results 
of  practice  have  justified  the  use  of  gelatin  in 
the  food.  Unfortunately  I  have  no  studies  so 
conducted    as    to    enable    me    to    make    an   un- 

*  This  is  the  form  of  gelatin  which  I  have  commonly  employed. 
It  may  be  mentioned  that  Dr.  Wakeman  found  it  to  contain  0.74 
per  cent,  of  calcium  oxide  and  a  trace  of  magnesium. 


INFANTILISM  101 

equivocal  inference  that  a  gain  in  weight  has 
been  exclusively  attributable  to  the  addition 
of  gelatin  to  the  dietary,  but  I  have  observa- 
tions on  several  carefully  studied  cases  which 
make  me  think  this  probable.  The  case  in 
which  the  evidence  for  this  is  most  satisfac- 
tory is  that  of  a  child  of  two  years  with 
chronic  infection  with  B.  hifidus  and  B.  in- 
fantilis. Here  for  a  time  the  food  consisted 
exclusively  of  kumyss,  as  all  effort  to  give 
carbohydrate  food  caused  exacerbations  of 
diarrhoea.  On  this  diet  it  was  impossible  to 
secure  a  gain  in  weight.  The  addition  of 
15  grams  of  gelatin  daily  was  followed  by  a 
gain  in  weight,  which  ceased  when  the  gelatin 
was  stopped  and  again  recurred  when  it  was 
once  more  added  to  the  kumyss.  And  it  may 
be  remarked  in  passing  that  such  a  combina- 
tion of  a  fermented  milk  (thus  largely  ridding 
it  from  sugar)  with  gelatin  seems  to  constitute 
the  most  appropriate  treatment  in  some  acute 
and  subacute  ileo-colic  infections  of  childhood 
in  which  the  intolerance  for  carbohydrates 
occasions  a  serious  loss  in  weight  and  blocks 
the  path  to  recovery.  It  is  perhaps  worth 
mentioning  in  this  connection  that  both  B. 
hifidus  and  B,  infantilis  may  be  regarded  as 
practically  uncultivable  on  ordinary  gelatin 
media.  We  may  reasonably  ask  ourselves  if 
one    of   the    advantages    of   gelatin    as    a    food 


102  INFANTILISM 

may  not  be  due  in  part  to  the  failure  of  these 
and  some  other  acidophile  bacteria  to  grow  on 
this  type  of  protein. 

It  is  somewhat  helpful  in  formulating  our 
indications  for  the  use  of  gelatin  to  think  of 
this  food  in  its  various  substituent  relations 
to  the  different  types  of  foodstuffs.  Given  a 
full  protein  ration,  it  is  probably  true  that 
either  the  carbohydrates  alone  or  the  fats 
alone  may  be  substituted  wholly  by  gelatin, 
perhaps  not  indefinitely,  but  for  a  considerable 
time.  On  the  other  hand,  given  average  normal 
rations  of  fats  and  carbohydrates,  the  typical 
proteins  may  be  replaced  by  gelatin,  not 
wholly,  be  it  noted,  but  only  in  part.  To  what 
extent  these  proteins  can  be  substituted  by 
gelatin  has  been  much  discussed  and  is  still 
the  subject  of  experimental  inquiry.  Any  re- 
liable general  statement  on  this  important  point 
is  at  present  impossible.  Murlin^  made  an 
experiment  on  a  man  of  70  kilograms  net 
weight  and  receiving  a  diet  holding  ten  per 
cent,  more  than  the  fasting  requirement  of 
nitrogen  and  51  calories  per  kilogram  of 
potential  energy,  of  which  fully  two  thirds  were 
supplied  by  carbohydrates.  Under  these  con- 
ditions it  was  possible  to  supply  63  per  cent, 
of  the  total   nitrogen   as   gelatin   for   a   period 

***The  Nutritive  Value  of  Gelatin/*  I.  Amer.  Jour,  of 
Fhysiol.,  XIX,  No.  ill,  p.  285 


INFANTILISM  103 

of  two  days  and  still  to  maintain  a  small 
retention  of  nitrogen.^  I  do  not  know  any 
pathological  condition  in  which  I  would  recom- 
mend the  therapeutic  use  of  gelatin  in  quan- 
tities and  proportions  even  approximating  those 
used  in  the  experiment  just  mentioned.  A 
certain  disgust  arises  from  the  taking  of  large 
quantities  of  gelatin,  and  this  in  itself  limits 
its  use.  It  is  doubtful  if  most  adults  can 
tolerate  more  than  50  grams  of  gelatin  daily 
for  a  considerable  period,  and  many  cannot 
take  more  than  30  or  40  grams  without  de- 
veloping a  dislike.  Thus  we  are  in  general 
limited  in  using  gelatin  to  about  10  or  15  per 
cent,  of  the  total  caloric  requirements.  In 
using  this  proportion  of  gelatin  as  part  of  the 
dietary  of  a  patient  with  infantilism  it  is  always 
desirable  to  formulate  a  clear  conception  as 
to  the  reason  for  which  it  is  given  in  the 
individual  case — whether  mainly  to  replace  fats, 

^  It  appears  that  the  high  percentage  of  glycocoll  in  gelatin 
may  be  an  important  factor  in  this  retention  of  nitrogen,  which 
is  however  only  temporary.  This  temporary  character  of  the 
glycocoll  nitrogen  retention  may  help  to  explain  the  inadequacy 
of  gelatin  as  a  substitute  for  typical  protein  food.  See  Murlin, 
* '  The  Nutritive  Value  of  Gelatin, ' '  II.  Amer.  Jour.  Physiol.,  XX, 
No.  i,  p.  234. 

If  one  represents  the  protein  metabolism  in  starvation  by  one 
the  use  of  about  the  same  quantity  of  gelatin  reduces  the  protein 
waste  of  the  body  23  per  cent.  (Kirchmann:  Zeitschr.  f.  Biol., 
XL,  p.  54,  1900.) 

In  sparing  protein  small  quantities  of  gelatin  appear  to  have 
about  as  much  effect  as  larger  amounts. 


104  INFANTILISM 

carbohydrates  or  proteins.  In  a  case  where 
carbohydrates  and  fats  are  tolerated  in  fair 
amount  without  disturbance  the  use  of  gelatin 
should  be  regarded  as  a  means  of  reducing 
the  requirements  of  ordinary  protein  food  with 
a  view  to  limiting  intestinal  putrefaction  based 
on  the  breakdown  of  tryptophan  and  tyro  sin. 
On  the  other  hand,  where  carbohydrates  must 
be  used  sparingly  or  fats  are  badly  resorbed, 
or  where  both  these  conditions  prevail,  gelatin 
should  be  utilized  with  a  view  to  replacing  in 
part  either  or  both  these  foodstuffs,  but  with- 
out reducing  the  ordinary  protein  nitrogen 
below  a  fair  average  requirement. 

Thus  we  may  summarize  as  follows  the 
qualities  for  which  gelatin  can  be  recommended 
as  a  foodstuff  in  cases  of  infantilism:  (1)  a 
considerable  degree  of  caloric  value,  (2)  as  a 
partial  substitute  for  carbohydrates,  fats  or 
common  proteins,  (3)  as  incapable  of  under- 
going putrefaction  based  on  the  presence  of 
the  tryptophan  or  tyro  sin  molecules,  (4)  on 
account  of  prompt  absorption,  and  (5)  owing 
to  its  inability  to  support  certain  specific 
forms  of  bacterial  life  associated  with  this 
disease. 

Finally,  in  reference  to  diet,  the  following 
example  may  be  given.  The  following  dietary 
was  successfully  employed  in  Case  I  during 
several     critical    months,    that    is,     while    the 


INFANTILISM  105 

transition  was  being  made  frona  a  condition 
of  stationary  weight  to  one  of  uninterrupted 
gains  in  weight.  This  dietary  was  subsequently 
modified  by  reducing  its  content  of  fat  by  the 
addition  of  small  quantities  of  whiskey  and 
by  some  minor  changes. 

Brealcfast,  6:30 — 7:00  A.  M.  6  ounces  milk  with  gelatin 

1  Huntley  &  Palmer  biscuit 
Lunch,  9:30  A.  M.                                6  ounces  milk  with  gelatin 

2  Huntley  &  Palmer  biscuits 
Dinner,  1:30  p.  m.                              Scraped    beef    and    juice    (one 

tablespoonful  of  each) 
1  tablespoonful  vegetable* 
1  tablespoonful  rice 

1  Huntley  &  Palmer  biscuit 
Afternoon  Lunch,  4:30  P.  m.  6  ounces  broth  with  gelatin 
Supper,  6:30  p.  M.                              1  tablespoonful  rice 

6  ounces  milk  with  gelatin 

2  Huntley  &  Palmer  biscuits 
Total  quantity  milk  daily,  18  ounces 

Total  broth  daily  (beef  tea,  chicken  or  mutton  broth),  6  ounces 

Total  rice  daily,  2  tablespoonfuls 

Total  Huntley  &  Palmer  biscuits  daily,  6 

Total  gelatin  daily  (Cox's),  1  box  (about  1  ounce) 

Beef  juice  from  1  lb.  round  of  beef,  daily 

I    have    calculated   that   the    caloric   value    of    this    dietary    la 

approximately  as  follows: 

Fat 342  calories 

Proteins 205  calories 

Gelatin 120  calories 

Carbohydrates 480  calories 

1147  calories 
*The  vegetables  used  were  spinach,   string  beans,  carrots  and 
peas.     It   was  necessary   at   times   to    eliminate   these  vegetables 
entirely  from  the  dietary  for  short  periods  of  time,  as  they  act  in 
an  irritative  way. 

These  figures   are   based   on   the    assumption 
that  the  patient  got  in   this   dietary  38   grams 


106  INFANTILISM 

of  fat,  8  grams  nitrogen  in  the  form  of  pro- 
teins, other  than  gelatin,  30  grams  gelatin,  27 
grams  milk  sugar,  and  from  90  to  100  grams 
of  starch  and  dextrine,  in  the  form  of  Huntley 
&  Palmer  biscuits,  rice,  vegetables,  broths,  etc. 
The  assumption  that  the  caloric  value  of  this 
diet  is  about  1150  calories  cannot  be  far  from 
the  truth.  By  changes  subsequently  made  and 
mentioned  above,  this  caloric  value  was  re- 
duced to  about  1100  calories. 

I  am  inclined  to  think  the  above  dietary 
might  be  criticized  as  containing  an  excess  of 
proteins.  The  excess  is,  however,  much  less 
now  than  when  the  patient  first  came  under 
observation,  for  it  is  obvious  that  an  excess 
of  proteins  for  a  child  weighing  25  pounds  is 
considerably  less  excessive  for  a  child  weighing 
31  pounds.  I  am,  however,  disposed  to  think 
that  the  protein  is  still  from  20  to  25  per 
cent,  in  excess  of  an  ideal  diet,  but  I  have 
not  reduced  it  simply  because  the  patient  is 
doing  so  well  that  I  am  disposed  to  let  well 
enough  alone.  I  shall,  however,  consider  it 
proper  to  make  a  slow  reduction  in  the  pro- 
teins if  I  cannot  otherwise  satisfactorily  reduce 
the  quantity  of  putrefactive  products  in  the 
urine. 

Pharmacological    Measures 

Although  pharmacological  measures  do  not 
have  a  large   share  in  the  treatment  of  intes- 


INFANTILISM  107 

tinal  infantilism  there  are  a  few  topics  which 
require  at  least  a  mention  in  this  connection. 
These  are  the  use  of  iron,  the  use  of  alcohol, 
the  employment  of  cathartic  and  antiseptic 
medicaments  and  the  administration  of  calcium 
and  magnesium  salts  and  of  phosphoric  acid. 
I  believe  that  in  general  iron  preparations  are 
not  well  tolerated  by  the  stomachs  of  these 
patients  and  that  it  is  better  to  avoid  their 
use.  It  is  also  to  be  questioned  whether  iron 
is  helpful  for  the  amelioration  of  the  asso- 
ciated anaemia.  It  is  certain  that  the  anaemia 
may  greatly  improve  as  the  result  of  the  insti- 
tution of  a  suitable  diet,  without  the  aid  of 
drugs.  The  objection  to  the  use  of  iron  appears 
to  me  extremely  well  defined  during  the  period 
of  absolute  arrest  of  growth.  When  growth 
has  begun  anew  and  is  progressing  in  a  satis- 
factory way  iron  preparations  may  be  em- 
ployed with  benefit  to  a  persistent  anaemia,  and 
even  without  noticeable  detrimental  effect  on 
digestion.  It  is  desirable  to  employ  the  least 
irritant  preparations  and  to  desist  promptly 
when  increased   digestive   disturbances   occur. 

The  administration  of  from  5  c.c.  to  10  c.c. 
of  whiskey  with  the  milk,  kumyss  or  broth 
may  prove  a  helpful  measure  where  the  hands 
and  feet  are  persistently  cold  and  the  peri- 
pheral circulation  is  feeble.  In  warm  weather 
the  alcohol  should  be  omitted  except,  perhaps, 


108  INFANTILISM 

in  the  morning.  The  doses  just  mentioned  may 
be  repeated  three  or  four  times  daily  in  some 
instances. 

As  to  the  use  of  cathartics  it  is  certain  that 
they  should  always  be  sparingly  employed  and 
not  frequently.  It  is  not  clear  that  they 
accomplish  any  unmixed  good.  Small  doses  of 
calomel  may  be  used  from  time  to  time  to 
bring  away  the  considerable  quantities  of 
mucus  which  accumulate  in  the  upper  colon  or 
to  bring  away  putrefactive  products  which  have 
been  suspected  to  accumulate.  The  good  that 
is  accomplished  by  such  evacuations  is  com- 
monly balanced  in  part  by  some  prostrating 
effect  of  the  cathartic  and  the  disturbance  of 
regular  intestinal  habits.  I  am  disposed  to 
believe  that  the  chief  legitimate  use  of  cathartics 
arises  when  there  has  been  an  error  of  diet, 
but  as  such  errors  are  very  largely  avoidable, 
the  resort  to  cathartic  medicaments  should  be 
rare.  Where  the  rapid  diminution  of  putre- 
faction is  required,  a  quickly  acting  cathartic, 
such  as  castor  oil,  is  probably  the  most  effective 
remedy.  I  have  little  faith  in  the  use  of 
intestinal  antiseptics  in  the  management  of  in- 
fantilism and  think  we  should  avoid  experi- 
menting with  them,  at  least  until  we  get  a 
more  rational  basis  for  their  use  than  at 
present  exists,  and  can  feel  assured  that  those 
we   try   are    harmless.    Yet   it   is    possible   the 


INFANTILISM  109 

future  will  teach  us  something  about  the  rational 
use   of    suitable   antiseptics. 

Where    defective    absorption   of   calcium    and 
magnesium   is   so   conspicuous   a   feature    as    in 
the  processes  underlying  infantilism,  it  becomes 
essential    for   us    to   inform    ourselves   fully   as 
to   the   conditions  that  promote  the   absorption 
of   salts   of  the   alkali   earths.    At  present   our 
knowledge  on  this  important  point  is  far  from 
satisfactory.    What  can  we  do  to  secure  better 
absorption    of    lime    and    magnesium    salts?    I 
have    already    indicated    my    belief    that    those 
conditions  which  mitigate  the  inflammatory  state 
of  the   small   intestine   are  those   that   lead  to 
spontaneous  improved  absorption.    But  we  may 
not  be  able  to  wait  patiently  for  this  improve- 
ment;   we    may   feel    obliged    to    do    something 
to  secure  a  larger  absorption  of  salts  by  offer- 
ing  the   mucous   membrane   of   the   intestine    a 
larger    or    wider    choice    of    alkali    earth    com- 
pounds.   Physicians   frequently    do   in   fact   at- 
tempt this.     One  way  of  so  doing  is  by  giving 
the    patient    those    salts    which    occur    in    the 
bones,  especially  the  phosphates  and  carbonates 
of  calcium  and  magnesium.    As  to  the  efficacy 
of  such  attempts  we  know  nothing  definite,  but 
are    warranted    in    suspecting    that    they    are 
largely  futile.    Since  the  feces  contain  an  excess 
of  phosphates  of  the  alkali  earths  in  infantilism, 
it  is  clear  that  the  intestine  must  have  chances 


110  INFANTILISM 

to  take  up  these  salts,  but  fails  to  use  them. 
In  healthy  young  dogs  (and  presumably  in 
children)  the  normal  mucous  membrane  appar- 
ently takes  up  inorganic  tricalcium  phosphate 
as  well  as  the  calcium  salts  of  milk.^  But 
under  the  pathological  conditions  of  infantilism 
there  is  no  reason  to  suppose  that  calcium 
phosphate  would  have  any  different  fate  from 
the  calcium  salts  of  the  milk,  which  we  know 
to  be  imperfectly  absorbed.  Possibly  one  factor 
in  the  defect  of  absorption  is  the  failure  of 
the  gastric  juice  to  secrete  hydrochloric  acid 
in  adequate  quantity, — a  function  which  must 
facilitate  the  absorption  of  calcium  and  mag- 
nesium through  the  gradual  formation  of  the 
chlorides.  However  this  may  be  in  fact,  we 
shall  do  well  to  give  our  alkali  earth  salts  in 
soluble  form.  For  this  purpose  the  lactates  of 
calcium  and  magnesium  may  be  used.  From 
20  to  40  milligrams  of  calcium  lactate  may  be 
given  in  aqueous  solution  in  the  food  three 
times  daily  without  any  detrimental  effects.  I 
do  not  think  we  are  justified  in  stating  posi- 
tively that  this  is  a  truly  efficacious  method  of 
securing  an  improved  absorption  in  marked 
cases  of  chronic  enteritis,  but  it  probably  is 
the  best  method   at  our  disposal.    It  deserves 

"Hans  Aron  and  Karl  Frese.     Biochem.  Zeitschr.,  IX,  pp.  185- 
207,  1908. 


INFANTILISM  111 

to     be    experimentally    worked    out    with    the 
utmost  care. 

Finally  a  word  should  be  said  on  the  admin- 
istration of  phosphoric  acid.  It  is  as  important 
to  give  phosphoric  acid  as  to  give  calcium  and 
magnesium  where  the  skeleton  is  retarded,  but 
the  acid  should  be  given  separately  from  the 
alkali  earths  in  order  to  avoid  the  precipita- 
tion of  insoluble  phosphates  in  the  lumen  of 
the  gut.  Where  the  stomach  is  not  sensitive 
the  acid  sodium  phosphate  may  be  given,  but 
where  this  difficulty  does  exist  the  dilute  phos- 
phoric  acid  may  be  given  before  meals. 

I  shall  not  attempt  to  discuss  here  the  use 
of  fermented  milks  because  I  do  not  at  present 
possess  the  necessary  data.  I  am,  however, 
making  experimental  observations  on  this  sub- 
ject and  hope  before  long  to  consider  it 
systematically. 

It  is  believed  that  the  foregoing  considera- 
tions regarding  the  pathology  and  management 
of  intestinal  infantilism  justify  the  conclusion 
that  the  outlook  for  the  amelioration  of  extreme 
cases  of  this  affection  is  in  reality  much  better 
than  might  be  supposed  from  the  results  com- 
monly obtained.  The  task  of  management  is 
at  best  a  tedious  one,  but  it  is  one  which 
repays  deliberate  effort,  both  in  the  variety  of 
scientific  interest  it  affords  and  in  the  satis- 
faction it  yields  through  its  practical  successes. 


112  INFANTILISM 

It  is  essential  to  realize  clearly  that  rapid 
recoveries  are  not  to  be  expected  under  any 
circumstances,  after  a  state  of  true  infantilism 
has  been  developed.  Moreover  it  will  be  a 
help  to  recognize  that  the  process  of  recovery 
may  very  properly  be  regarded  as  made  up  of 
two  distinct  stages.  The  first  stage  is  one  of 
improved  nervous  and  digestive  conditions,  with 
signs  of  diminishing  intoxication.  In  this  stage 
there  is  little  or  no  gain  in  weight  although 
there  may  be  a  slight  improvement  in  strength. 
This  stage  may  last  from  three  months  to  a 
year.  At  the  end  of  this  time  the  patient 
begins  to  gain  distinctly  in  weight  as  well  as 
to  continue  growing  in  strength,  and  when 
this  occurs  an  uninterrupted  improvement  may 
be  reasonably  looked  for.  The  important  thing 
is  to  understand  that  improved  bacterial  con- 
ditions must  precede  by  a  considerable  time  a 
significant  gain  in  weight. 

Conclusions 

In  view  of  the  many  details  which  it  has 
been  necessary  to  incorporate  in  this  study  of 
infantilism,  it  seems  to  me  desirable  to  sum- 
marize the  chief  conclusions  which  may  be 
drawn. 

The  following  are  the  facts  which  I  would 
especially    emphasize : 


INFANTILISM  113 

1.  There  is  a  pathological  state  of  child- 
hood marked  by  a  striking  retardation  in 
growth  of  the  skeleton,  the  muscles  and  the 
various  organs  and  associated  with  a  chronic 
intestinal  infection  characterized  by  the  over- 
growth and  persistence  of  bacterial  flora  belong- 
ing normally  to  the  nursling  period.  To  this 
condition  may  be  applied  the  term  Intestinal 
Infantilism. 

2.  The  chief  manifestations  of  intestinal 
infantilism  are  arrest  in  the  development  of 
the  body;  maintenance  of  good  mental  powers 
and  a  fair  development  of  the  brain;  marked 
abdominal  distension;  a  slight  or  moderate  or 
considerable  degree  of  simple  anaemia;  the 
rapid  onset  of  physical  and  mental  fatigue; 
irregularities  of  intestinal  digestion  resulting 
in  frequent  diarrhoeal  seizures.  Clinical  fea- 
tures of  secondary  importance  are  excessive 
appetite,  various  minor  signs  of  nervous  in- 
stability, a  subnormal  temperature,  cold  hands 
and   feet,   and    slight   signs    of   rickets. 

3.  A  study  of  the  bacterial  flora  of  the 
intestinal  tract  in  cases  of  infantilism  shows 
that  the  dominant  bacteria  of  the  upper  and 
lower  colon  and  probably  of  the  ileum  are 
largely  Gram-positive  organisms  belonging  to 
the  groups  of  organisms  which  may  be  desig- 
nated as  the  Bacillus  hifidus  type,  the  Bacillus 
infantilis    type    and    the    coccal     type.    It    is 


114  INFANTILISM 

impossible  to  say  to  what  extent  B,  hifidus 
and  B,  infantilis  constitute  the  dominant  types, 
partly  because  of  the  difficulty  in  forming 
reliable  estimates  of  the  quantitative  relations 
between  these  organisms,  partly  because  they 
vary  in  the  same  individual  under  different 
conditions  of  diet  and  at  different  stages  of 
the  disease.  Noteworthy  is  the  absence  of 
organisms  of  the  B,  coli  and  B,  lactis  aero- 
genes  type,  not  only  from  the  feces  but  from 
material  collected  through  the  use  of  a  cathartic. 
The  dominance  of  these  Gram-positive  organ- 
isms relates,  however,  only  to  infantilism  in 
its  incipiency  and  at  its  height. 

4.  Among  the  urinary  expressions  of  the 
bacterial  state  associated  with  intestinal  in- 
fantilism is  to  be  constantly  found  an  excess 
of  putrefactive  products  of  intestinal  origin. 
Prominent  among  these  are  indican  and  phenol 
compounds.  At  times  indolacetic  acid  is  a 
prominent  putrefactive  product.  Sometimes  the 
aromatic   oxyacids    are   much  in   excess. 

5.  Among  the  characteristic  features  relat- 
ing to  the  intestinal  contents  are  the  presence 
of  neutral  fat,  fatty  acids  and  soaps  in  marked 
excess,  pointing  to  impaired  fat  absorption. 
With  this  condition  is  associated  usually  an 
increase  of  mucus  and  other  evidence  of  excessive 
desquamation  of  epithelial  elements. 


INFANTILISM  115 

6.  A  careful  study  of  the  calcium  and 
magnesium  balances  in  one  of  our  cases  (Case  I) 
showed  failure  of  normal  resorption  of  calcium 
and  magnesium,  thus  accounting  for  the  failure 
of  skeletal  growth.  The  amount  of  calcium 
lost  by  the  feces  as  soaps  of  calcium  was 
sufficient  to  have  furnished  a  fair  skeletal 
growth  had  these  calcium  soaps  been  absorbed 
instead  of  lost.  It  is  a  practical  certainty  that 
the  loss  of  calcium  and  magnesium  through 
the  feces  is  the  explanation  of  the  impaired 
skeletal   growth  in  intestinal   infantilism. 

7.  In  the  pathology  of  intestinal  infantilism 
two  leading  features  call  for  explanation — 
first,  the  retardation  of  growth;  second,  the 
chronic  intoxication.  The  retardation  in  growth 
can  apparently  be  explained  on  the  basis  of 
the  imperfect  absorption  of  nutritive  material 
which  can  be  demonstrated  in  these  cases. 
This  impaired  absorption  of  foodstuffs  is 
probably  to  be  ascribed  to  a  chronic  inflamma- 
tion located  in  the  ileum  and  colon  and  asso- 
ciated with  the  presence  of  abnormal  forms  of 
bacteria.  The  intoxication  which  is  so  promi- 
nent a  feature  of  intestinal  infantilism  at  its 
height  may  confidently  be  ascribed  to  the  action 
of  putrefactive  products  of  intestinal  origin 
upon  the  central  nervous  system  and  muscles. 
The  exact  relation  of  the  abnormal  bacterial 
flora  to  the  pathological   conditions  in  the  in- 


116  INFANTILISM 

testine  is  not  yet  clear.  The  chief  evidence  in 
favor  of  the  causal  relationship  between  the 
phenomena  of  infantilism  and  the  overgrowth 
and  persistence  of  flora  of  the  nursling  period, 
especially  B,  hifidus,  is  fonnd  in  the  changes 
that  occur  during  convalescence  when  these 
organisms  are  gradually  replaced  by  those  of 
the  type  appropriate  to  childhood.  A  further 
evidence  in  the  same  direction  is  seen  in  the 
great  increase  in  the  infantile  types  of  bac- 
teria during  periods  of  relapse.  There  is  no 
evidence  at  present  that  intestinal  infantilism 
has  any  other  origin  than  a  purely  intestinal 
one. 

8.  There  is  a  condition  of  acute  or  subacute 
infection  of  the  intestinal  tract  in  early  infancy 
which  leads  to  great  losses  in  weight  and 
strength,  the  persistence  of  which  is  a  probable 
cause  of  chronic  infantilism.  This  condition, 
like  chronic  infantilism,  is  associated  with  the 
dominance  of  Gram-positive  microorganisms  in 
the  intestinal  tract,  mainly  those  belonging  to 
the  groups  of  B.  hifidus  and  B,  infantilis,  or 
certain  other  acidophile  bacteria  which  are 
closely  related.  The  bacterial  conditions  of  this 
acute  or  subacute  infection,  if  not  identical 
with  those  of  chronic  infantilism,  are  never- 
theless very  similar,  and  this  is  a  further 
reason  for   regarding   the  chronic   condition  as 


INFANTILISM  117 

the    outcome    of    the    more    acute    state    just 
mentioned. 

9.  The  state  of  intestinal  infantilism  is  a 
very  persistent  one  and  not  likely  to  be  fol- 
lowed by  normal  growth  except  as  the  result 
of  careful  therapeutic  interference.  A  certain 
proportion  of  such  infantilism  children  die  from 
acute  infections  of  the  intestine;  others  are  per- 
manently retarded  in  growth,  which  leads  to 
pronounced  dwarfism. 

10.  Eational  therapeutic  interference  in  cases 
of  chronic  intestinal  infantilism  offers  hope  of 
the  reestablishment  of  the  processes  of  growth 
even  in  cases  in  which  the  bodily  arrest  has 
been  extreme  and  of  long  duration.  If  it  is 
too  much  to  say  that  the  most  satisfactory 
methods  of  treatment  are  now  known,  it  may 
be  claimed,  at  least,  that  we  are  in  possession 
of  certain  principles  of  treatment  which,  when 
carefully  applied,  are  likely  to  yield  better 
results  than  any  that  have  heretofore  been 
employed. 

11.  Temporary  relapses  are  very  common 
in  the  course  of  this  disease,  even  when  great 
care  is  being  taken  to  prevent  them.  The 
most  frequent  cause  of  such  relapses  is  the 
attempt  to  encourage  growth  by  the  use  of 
increased  amounts  of  carbohydrates.  When  a 
relapse  occurs  the  feces  become  voluminous, 
lose  their  conglomerate  appearance  and  become 


118  INFANTILISM 

of  lighter  color.  They  show  the  presence  of 
coccal  forms  in  excessive  numbers  and  there 
is  in  persistent  relapses  a  return  of  B,  in- 
fantilis and  B.  hifidus.  Any  disturbance  of 
digestion  which  checks  growth  or  causes  loss 
in  weight  is  to  be   accounted   a   relapse. 

12.  A  permanently  undersized  individual  is 
the  outcome,  even  in  the  most  favorably  pro- 
gressing instances,  of  the  severe  form  of 
infantilism.  This  condition  is  not  incompatible 
with  a  high  degree  of  mental  development. 


The  Common  Bacterial  Infections  of  the 

Digestive  Tract 

And  the  Intoxications  arising  from  them 

By  C.  A.  HERTER,  M.D. 

Professor  in  Pharmacology  and  Therapeutics  in 
Columbia  University 

Clothe  360  pages,  l2mo,  $l.SO  net 

"Now  that  it  has  been  clearly  shown  how  large  is  the  part 
played  by  the  intestinal  flora  in  many  apparently  remote  morbid 
processes,  the'appearance  of  the  present  volume  is  to  be  regarded  as 
a  boon  to  the  profession.  It  is  especially  valuable,  however,  not 
alone  from  the  fact  that  it  ofifers  a  summary  of  what  has  been  learned 
from  and  is  suggested  by  the  work  of  others  in  this  field,  but  in  that 
it  comprises  the  results  of  the  enormous  amount  of  original  work 
relating  to  the  subject  carried  out  in  the  author's  laboratory,  and 
contains  a  wealth  of  new  information  that  seems  destmed  to  form 
what  may  almost  be  termed  a  new  point  of  departure  in  diagnosis 
and  treatment." — Medical  Record. 

"The  methods  of  investigating  the  digestive  tract  outlined  in 
this  volume  will  prove  valuable  to  the  practitioner  who  would  de- 
termine the  presence  of  abnormal  bacterial  processes  before  the 
onset  of  the  clinical  signs  of  incurable  or  highly  refractory  states  of 
intoxication— and  this  is  the  all-sufficient  raison  d'etre  for  the  book. 
Considerable  stress  has  been  laid  by  the  author  on  methods  developed 
in  his  laboratory,  in  the  belief  that  their  painstaking  application  will 
furnish  practitioners  with  reliable  indications  as  to  the  progress  of 
many  cases  of  infection  oi\.\iQ^\z^%\:\vt\x^zty  —Merck' s  Archives. 

"Those  to  whom  the  terminology  of  the  bacteriologist  is  not 
unfamihar  will  find  here  not  only  a  well  written  but  also  an  inter- 
esting and  suggestive  study  of  a  rich  fauna  and  a  discussion  of 
questions  of  much  import,  for  they  are  fundamental  in  relation  to 
a  great  human  woe,  indigestion.  Particularly  alluring  is  the  an- 
tagonism existing  between  different  bacteria,  the  opposition  of  the 
native  to  the  immigrant  forms."— 7%^  Nation. 

"Dr.  Herter's  book  is  bound  to  have  the  effect  of  broadening 
our  conception  of  the  subject  of  infectious  diseases  of  the  digestive 
tract,  and  deserves  a  wide  reading."— 6^^^?/'^^  C.  Whipple. 

Published  by 

THE  MACMILLAN  COMPANY 

<4-<«  FIFTH  AVENUE,  NEW  YORK 


A  SYSTEM  OF  MEDICINE 

By  Many  Writers,  edited  by  Thomas  Clifford  Allbutt, 
Regius  Professor  of  Physics  in  the  University  of  Cambridge ;  and 
Humphry  Davy  Rolleston,  Physician  to  St.  George's  Hospital 
and  to  the  Victoria  Hospital  for  Children,  London. 

SECOND  EDITION.  Thoroughly  revised  and  in  the  case 
of  many  articles  entirely  re-written.     NOW  READY: — 

Volume  I.     Prolegomena  ;  Fevers. 

Volume  II.  Parti.  Infectious  Diseases;  Intoxication. 
Part  2.  Tropical  Diseases :  Animal  Para- 
sites. 

Volume  III.  Diseases  of  Obscure  Origin  ;  Diseases  of  the 
Alimentary  Canal ;  and  Diseases  of  the 
Peritoneum. 

Volume  IV.    Parti.     Diseases   of   the   Liver,    Pancreas, 
Ductless  Glands,  and  Kidneys. 
Part  2.     Diseases    of    the    Nose,    Pharynx, 
Larynx  and  Ear.     In  Press. 

Volumes  V-X.    In  Preparation. 

Price  of  each  volume,  or  part.  Cloth,      -       -       $6.00  net. 

Half  morocco,         8.00  net. 

Opinions  by  Professional  Editors  in  Great  Britain. 

"As  a  whole,  the  work  is  one  of  which  the  profession  of 
medicine  in  this  country  may  well  be  proud,  and  one  which,  like 
its  predecessor,  will  be  of  great  value  to  the  investigator  and  the 
practitioner  who  desires  to  keep  himself  informed  of  the  advances 
in  medical  knowledge." — Lancet, 

"The  general  impression  conveyed  by  study  of  this  new 
edition  is  one  of  profound  admiration  for  its  general  excellence. 
.  .  .  All  the  articles  have  been  brought  up  to  date,  and,  in  addition 
to  the  clinical  aspects  of  the  various  diseases  dealt  with,  their 
pathology  is  so  exhaustively  treated  that  any  other  work  on  this 
subject  is  scarcely  necessary  to  a  man  with  the  System  on  his 
shelves.     The  extensive  bibliographies  are  extremely  valuable." 

— Medical  Chronicle. 

**As  full  and  complete  a  work  of  reference  as  the  most  expert 
writers  and  the  most  discriminating  of  editors  can  make  it.  ... 
A  work  which  presents  a  trustworthy  compendium  of  all  that  is 
really  known  upon  the  subjects  with  which  it  deals." 

— British  Medical  Journal. 

PUBLISHED  BY 

THE  MACMILLAN  COMPANY 

64-66  FIFTH  AVENUE,  NEW  YORK 


DUE  DATE 


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